bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost-effectiveness of empagliflozin in patients with type 2 diabetes and established cardiovascular disease in China
Authors: Ramos Mafalda , Men Peng , Wang Xu , Ustyugova Anastasia , Lamotte Mark
Published: August 2021

Background

In several cardiovascular outcome trials (CVOTs), empagliflozin (SGLT-2 inhibitor), sitagliptin (DPP-4 inhibitor) and liraglutide (GLP-1 receptor agonist) + standard of care (SoC) were compared to SoC in patients with type 2 diabetes and established cardiovascular disease (CVD). This study assessed the cost-effectiveness (CE) of empagliflozin + SoC in comparison to sitagliptin + SoC and liraglutide + SoC based on the respective CVOT.

Methods

The IQVIA Core Diabetes Model (CDM) was calibrated to reproduce the CVOT outcomes. EMPA-REG OUTCOME baseline characteristics and CVOT specific treatment effects on risk factors for cardiovascular disease (HbA1c, BMI, blood pressure, lipids) were applied. Three-year observed cardiovascular events of empagliflozin + SoC versus sitagliptin + SoC and liraglutide + SoC were derived from EMPA-REG OUTCOME and an indirect treatment comparison. Relative risk adjustments to calibrate the CDM were obtained after a trial and error process to match as closely the observed and CDM-predicted outcomes. The drug-specific treatment effects were considered up until HbA1c reached 8.5% and treatment switch occurred. After this switch, the United Kingdom Prospective Diabetes Study 82 risk equations predicted events based on co-existing risk factors and treatment intensification to basal bolus insulin were applied. The analysis was conducted from the perspective of the Chinese healthcare system applying 3% discounting. The time horizon was lifelong.

Results

Empagliflozin + SoC provides additional Quality Adjusted Life years (QALY + 0.564) for an incremental cost of 42,497RMB (US$6053) compared to sitagliptin + SoC, resulting in an Incremental Cost Utility Ratio of 75,349RMB (US$10,732), thus below the willingness-to-pay threshold of 212,676RMB, corresponding to three times the Gross Domestic Product in China (2019). Compared to liraglutide + SoC, empagliflozin + SoC use leads to 0.211QALY gained and cost savings of 71,427RMB (US$10,173) and is as such dominant. Scenario and probabilistic sensitivity analyses demonstrated the robustness of the results.

Conclusion

Results suggest that empagliflozin + SoC is cost-effective compared to sitagliptin + SoC and liraglutide + SoC at a willingness-to-pay threshold of 212,676RMB ($30,292)/QALY.
Strategies for reducing out of pocket payments in the health system: a scoping review
Authors: Jalali Faride Sadat , Bikineh Parisa , Delavari Sajad
Published: August 2021

Background

Direct out-of-pocket payments (OOP) are among the most important financing mechanisms in many health systems, especially in developing countries, adversely affecting equality and leading vulnerable groups to poverty. Therefore, this scoping review study was conducted to identify the strategies involving OOP reduction in health systems.

Methods

Articles published in English on strategies related to out-of-pocket payments were Searched and retrieved in the Web of Science, Scopus, PubMed, and Embase databases between January 2000 and November 2020, following PRISMA guidelines. As a result, 3710 papers were retrieved initially, and 40 were selected for full-text assessment.

Results

Out of 40 papers included, 22 (55%) and 18 (45%) of the study were conducted in developing and developed countries, respectively. The strategies were divided into four categories based on health system functions: health system stewardship, creating resources, health financing mechanisms, and delivering health services.As well, developing and developed countries applied different types of strategies to reduce OOP.

Conclusion

The present review identified some strategies that affect the OOP payments According to the health system functions framework. Considering the importance of stewardship, creating resources, the health financing mechanisms, and delivering health services in reducing OOP, this study could help policymakers make better decisions for reducing OOP expenditures.
Perceptions of family, community and religious leaders and acceptability for minimal invasive tissue sampling to identify the cause of death in under-five deaths and stillbirths in North India: a qualitative study
Authors: Das Manoja Kumar , Arora Narendra Kumar , Kaur Gurkirat , Malik Prikanksha , Kumari Mahisha , Joshi Shipra , Rasaily Reeta , Chellani Harish , Gaikwad Harsha , Debata Pradeep , Meena K. R.
Published: August 2021

Background

Minimal invasive tissue sampling (MITS) has emerged as a suitable alternative to complete diagnostic autopsy (CDA) for determination of the cause of death (CoD), due to feasibility and acceptability issues. A formative research was conducted to document the perceptions of parents, community and religious leaders on acceptability of MITS.

Methods

This qualitative study was conducted at and around the Safdarjung Hospital, Delhi, India. Participants for in-depth interview included the parents who had either child or neonatal death or stillbirth and the key community and religious representatives. The focus group discussions (FGDs) involved community members. Process of obtaining consent for MITS was observed. Data were analyzed inductively manually for emerging themes and codes.

Results

A total of 104 interviews (parents of deceased children, neonates or stillbirths, n = 93; community members, n = 8 and religious leaders, n = 7), 8 FGDs (n = 72) were conducted and process of obtaining consent for MITS (n = 27) was observed. The participants were positive and expressed willingness to accept MITS. The key determinants for acceptance of MITS were: (1) understanding and willingness to know the cause of death or stillbirth, (2) experience of the healthcare received and trust, (3) the religious and sociocultural norms. Parents and community favored for MITS over CDA when needed, especially where in cases with past stillbirths and child deaths. The experience of treatment, attitude and communication from healthcare providers emerged as important for consent. The decision making process was collective involving the elders and family. No religious leader was against the procedure, as both, the respect for the deceased and need for medical care were satisfied.

Conclusions

Largely, MITS appeared to be acceptable for identifying the causes of child deaths and stillbirths, if the parents and family are counseled appropriately considering the sociocultural and religious aspects. They perceived the quality of care, attitude and communication by the healthcare providers as critical factors for acceptance of MITS.
Implementing work-related Mental health guidelines in general PRacticE (IMPRovE): a protocol for a hybrid III parallel cluster randomised controlled trial
Authors: Mazza Danielle , Chakraborty Samantha , Camões-Costa Vera , Kenardy Justin , Brijnath Bianca , Mortimer Duncan , Enticott Joanne , Kidd Michael , Trevena Lyndal , Reid Sharon , Collie Alex
Published: August 2021

Background

The Clinical Guideline for the Diagnosis and Management of Work-related Mental Health Conditions in General Practice (the Guideline) was published in 2019. The objective of this trial is to implement the Guideline in general practice.

Trial design

Implementing work-related Mental health conditions in general PRacticE is a hybrid III, parallel cluster randomised controlled trial undertaken in Australia. Its primary aim is to assess the effectiveness of a complex intervention on the implementation of the Guideline in general practice. Secondary aims are to assess patient health and work outcomes, to evaluate the cost-effectiveness of the trial, and to develop a plan for sustainability.

Methods

A total of 86 GP clusters will be randomly allocated either to the intervention arm, where they will receive a complex intervention comprising academic detailing, enrolment in a community of practice and resources, or to the control arm, where they will not receive the intervention. GP guideline concordance will be assessed at baseline and 9 months using virtual simulated patient scenarios. Patients who meet the eligibility criteria (>18years, employed, and receiving care from a participating GP for a suspected or confirmed work-related mental health condition) will be invited to complete surveys about their health and work participation and provide access to their health service use data. Data on health service use and work participation compensation claim data will be combined with measures of guideline concordance and patient outcomes to inform an economic evaluation. A realist evaluation will be conducted to inform the development of a plan for sustainability.

Results

We anticipate that GPs who receive the intervention will have higher guideline concordance than GPs in the control group. We also anticipate that higher concordance will translate to better health and return-to-work outcomes for patients, as well as cost-savings to society.

Conclusions

The trial builds on a body of work defining the role of GPs in compensable injury, exploring their concerns, and developing evidence-based guidelines to address them. Implementation of these guidelines has the potential to deliver improvements in GP care, patient health, and return-to-work outcomes.

Trial registration

ACTRN12620001163998, November 2020
Minocycline black bone disease in arthroplasty: a systematic review
Authors: Steadman William , Brown Zak , Wall Christopher J.
Published: August 2021

Background

Minocycline black bone disease is a rare finding that can cause concern when unexpectedly encountered during routine arthroplasty. Prolonged minocycline use can cause selective staining of subchondral bone, whilst peri-articular soft tissue and cartilage appear uninvolved.

Methods

A systematic review according to PRISMA guidelines was performed to identify all reported cases in the literature.

Results

Including the patient we present, eleven cases of minocycline black bone disease encountered during arthroplasty have been reported in the literature. All cases have had an excellent outcome, with no complications reported to date.

Conclusions

Minocycline black bone disease can be a concerning intra-operative finding when unexpectedly encountered during routine arthroplasty, but should not affect the operative plan. Surgeons should exclude alternative causes of bone discolouration when the history is unclear.
Aortic prosthetic size predictor in aortic valve replacement
Authors: Vo Anh Tuan , Nakajima Tomomi , Nguyen Trang Thi Thu , Nguyen Nguyen Thoi Hai , Le Nga Bich , Cao Tri Huu , Nguyen Dinh Hoang
Published: August 2021

Background

Patient-prosthesis mismatch (PPM) is a major concern in aortic valve replacement (AVR) and leads to perioperative morbidity and rehospitalization. Predicting aortic annulus diameter pre-procedurally is crucial to managing patients with high-risk of PPM.

Objectives

To compare preoperative measurements of aortic annulus from echocardiography and CT scan with surgical sizing and develop an imaging-based algorithm to predict PPM.

Methods

From January 2017 to December 2020, patients underwent AVR at a teaching hospital were examined. The relationship between imaging measurements with operative values was assesed using scatter plots and Pearson’s correlation coefficient. Univariable linear regression was then used to build the predictive model.

Results

A total of 144 patients underwent AVR during the study period. Suture types and surgical approaches were not significantly associated with prosthesis size. CT scan-based measurements showed strong correlation with prosthesis size: mean diameter (R = 0.79), perimeter-derived diameter (R = 0.76), and area-derived diameter (R = 0.75). Mechanical valve and tissue valve shared similar correlation coefficients. Prosthesis size predictive models based on CT scan were 12.89 + 0.335 × d for mean diameter, 13.275 + 0.315 × d for perimeter-derived diameter and 13.626 + 0.309 × d for area-derived diameter.

Conclusions

Preoperative CT scan measurements are a reliable predictor of aortic prosthesis size. Transthoracic echocardiography is a possible alternative, though it is highly performer-dependent and unable to represent the aortic annulus fully. Together, these two imaging modalities can be used to quantitatively anticipate PPM preoperatively.
Two methoxy derivatives of resveratrol, 3,3′,4,5′-tetramethoxy-trans-stilbene and 3,4′,5-trimethoxy-trans-stilbene, suppress lipopolysaccharide-induced inflammation through inactivation of MAPK and NF-κB pathways in RAW 264.7 cells
Authors: Zhou Chunxiu , Zhang Xutao , Ruan Cheng-Chao , Cheang Wai San
Published: August 2021

Background

3,3′,4,5′-tetramethoxy-trans-stilbene (3,3′,4,5′-TMS) and 3,4′,5-trimethoxy-trans-stilbene (3,4′,5-TMS) are two methoxy derivatives of resveratrol. Previous researches have proved that resveratrol and its analogues have anti-inflammatory effect through suppressing mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. This study aims to study whether 3,3′,4,5′-TMS and 3,4′,5-TMS alleviate inflammation and the underlying mechanism.

Methods

RAW 264.7 macrophage cells were treated with lipopolysaccharide (LPS) to induce inflammation and pretreated with 3,3′,4,5′-TMS or 3,4′,5-TMS. Cell viability was measured with the 3-(4,5)-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Nitric oxide (NO) release was detected by Griess reagent. The secretions of pro-inflammatory cytokines were assessed by ELISA kits. Protein expressions of signaling molecules were determined by Western blotting. Reactive oxygen species (ROS) production was detected by fluorescence staining and malondialdehyde (MDA) assay.

Results

3,3′,4,5′-TMS and 3,4′,5-TMS suppressed LPS-induced NO release and pro-inflammatory cytokines (IL-6 and TNF-α) secretions in a dose-dependent manner in RAW 264.7 cells. 3,3′,4,5′-TMS and 3,4′,5-TMS significantly down-regulated the LPS-induced expressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), and partially suppressed the activation of MAPK (phosphorylation of p38, JNK, ERK), and NF-κB (phosphorylation of IKKα/β, p65 and IκBα) signaling pathways; where phosphorylation of ERK and p65 was mildly but not significantly decreased by 3,3′,4,5′-TMS. LPS-induced NF-κB/p65 nuclear translocation was inhibited by both 3,3′,4,5′-TMS and 3,4′,5-TMS. Moreover, both resveratrol derivatives decreased the ROS levels.

Conclusions

3,3′,4,5′-TMS and 3,4′,5-TMS significantly suppress LPS-induced inflammation in RAW 264.7 cells through inhibition of MAPK and NF-κB signaling pathways and also provide anti-oxidative effect. This study reveals potential therapeutic applications of 3,3′,4,5′-TMS and 3,4′,5-TMS for inflammatory diseases.
Outcomes of community-based suicide prevention program in primary health care of Iran
Authors: Azizi Hosein , Fakhari Ali , Farahbakhsh Mostafa , Esmaeili Elham Davtalab , Mirzapour Mohammad
Published: August 2021

Background

Suicidal management and prevention in communities, especially in its first stages, is an effective intervention for the health systems. However, in numerous societies most cases go undetected. Primary Health Care (PHC) is an effective place for the management of Suicide Prevention Programs (SPP). In Malekan County, a health community assessment found suicide as the most important health problem. A regional SPP was performed for suicide prevention during 2014–2017.

Methods

This study was carried out in six steps: (1) Establishing a research team, (2) Improving a registry for suicidal behaviors (SBs), (3) Identifying local determinants of SBs, (4) Training healthcare providers, (5) Follow-up and monitoring of SBs, and (6) Public awareness campaigns. Our ultimate goal was to lower the rates of suicide, and suicide attempt (SA) by 15 and 20 %, respectively. Multiple logistic regression was used to estimate the adjusted odds ratios and the 95% confidence intervals.

Results

A total of 821 SAs and 32 suicides were identified. The gender distribution for suicides was 70% males whereas SAs were 64% among females. The majority of suicides occurred in spring 18 (56.25%) while summer was the most common season among SAs 288 (35.8%). Almost 62 and 75% of suicides and SAs have used hanging and poisoning methods, respectively. Hanging increased suicide risk significantly (OR: 8.5, 95% CI 2.9–76.99). During the study, 93 life-skill and parenting education sessions were held. The incidence rates of suicide and SA decreased from 11.22, and 203 per 100,000 in 2013 to 2.63, and 157 in 2017, respectively. Similarly, the re-attempt to SAs ratio decreased from 12% to 2013 to 6.7% in 2017. Moreover, more than 8% of SBs were collected from adjacent Counties.

Conclusions

At the study end, suicide, SA, and re-attempt were lowered by 75%, 22%, and 42%, respectively. The practical framework that achieved in this study could be used as a basis for developing future SPPs and suicide researches in the Iranian context. Furthermore, the various socio-economic and socio-cultural challenges highlight the need to consider a wide range of contextual factors when developing an SPP.
NUAK2 and RCan2 participate in the p53 mutant pro-tumorigenic network
Authors: Mammarella Eleonora , Zampieri Carlotta , Panatta Emanuele , Melino Gerry , Amelio Ivano
Published: August 2021

Most inactivating mutations in TP53 gene generates neomorphic forms of p53 proteins that experimental evidence and clinical observations suggest to exert gain-of-function effects. While massive effort has been deployed in the dissection of wild type p53 transcriptional programme, p53 mutant pro-tumorigenic gene network is still largely elusive. To help dissecting the molecular basis of p53 mutant GOF, we performed an analysis of a fully annotated genomic and transcriptomic human pancreatic adenocarcinoma to select candidate players of p53 mutant network on the basis their differential expression between p53 mutant and p53 wild-type cohorts and their prognostic value. We identified NUAK2 and RCan2 whose p53 mutant GOF-dependent regulation was further validated in pancreatic cancer cellular model. Our data demonstrated that p53R270H can physically bind RCan2 gene locus in regulatory regions corresponding to the chromatin permissive areas where known binding partners of p53 mutant, such as p63 and Srebp, bind. Overall, starting from clinically relevant data and progressing into experimental validation, our work suggests NUAK2 and RCan2 as novel candidate players of the p53 mutant pro-tumorigenic network whose prognostic and therapeutic interest might attract future studies.
Efficacy of low-load resistance training combined with blood flow restriction vs. high-load resistance training on sarcopenia among community-dwelling older Chinese people: study protocol for a 3-arm randomized controlled trial
Authors: Chen Nan , He Xiangfeng , Zhao Guoyun , Lu Linqian , Ainsworth Barbara E. , Liu Yu , Wu Xie
Published: August 2021

Background

Sarcopenia is accompanied by a decline in muscle mass, muscle strength, and muscle function. Resistance training is the most potential training method for the prevention and treatment of sarcopenia. However, the conventional high-load resistance training (CRT) recommended by the American College of Sports Medicine is a challenge for older people with sarcopenia. As a novel training method, low-load resistance training combined with blood flow restriction (LRT-BFR) may elicit similar muscle mass and muscle strength gains as CRT but with less effort. The objectives of this study are to assess and compare the efficacy and safety of 12-week LRT-BFR and CRT on muscle strength, muscle performance, body composition, pulmonary function, blood biomarkers, CVD risk factors, and quality of life in community-dwelling older Chinese people with sarcopenia.

Method

This is a 12-week, assessor-blinded, 3-arm randomized controlled trial with a non-exercise control group. Community-dwelling people over 65 years will be screened for sarcopenia according to the diagnostic criteria of the Asian Working Group for Sarcopenia (AWGS). Fifty-one subjects will be randomized into a LRT-BFR group (n= 17), a CRT group (n= 17), and a no-strength training control group (n= 17). The primary outcome is lower limb muscle strength. The secondary outcomes are body composition, upper limb muscle strength, pulmonary function, blood biomarkers, CVD risk factors, and quality of life. Post-intervention follow-up will be performed for 12 weeks. These indicators will be assessed at baseline (0 week), after the 12-week intervention (12 weeks), and at follow-up (24 weeks). The adverse events will also be reported. Data will be analyzed for all participants in an intent-to-treat plan.

Discussion

This study is the first RCT that will systematically measure and compare the efficacy and safety of LRT-BFR and CRT in older people with sarcopenia on muscle strength, body composition, pulmonary function, blood biomarkers (inflammatory biomarkers, hormone, and growth factors), CVD risk factors, and quality of life. This study can provide an efficient and safe method to prevent the progression of sarcopenia in older people.

Trial registration

Chinese Clinical Trial RegistryChiCTR2100042803. Registered on 28 January 2021.
Forecasting the carsharing service demand using uni and multivariable models
Authors: Alencar Victor Aquiles , Pessamilio Lucas Ribeiro , Rooke Felipe , Bernardino Heder Soares , Borges Vieira Alex
Published: August 2021

Carsharing is ana lternative to urban mobility that has been widely adopted recently. This service presents three main business models: two of these models base their services on stations while the remainder, the free-floating service, is free of fixed stations. Despite the notable advantages of carsharing, this service is prone to several problems, such as fleet imbalance due to the variance of the daily demand in large urban centers. Forecasting the demand for the service is a key task to deal with this issue. In this sense, in this work, we analyze the use of well-known techniques to forecast a carsharing service demand. More in deep, we evaluate the use of the Long Short-Term Memory (LSTM) and Prophet techniques to predict the demand of three real carsharing services. Moreover, we also evaluate seven state-of-the-art forecasting models on a given free-floating carsharing service, highlighting the potentials of each technique. In addition to historical carsharing service data, we have also used climatic series to enhance the forecasting. Indeed, the results of our analysis have shown that the addition of meteorological data improved the models’ performance. In this case, the mean absolute error of LSTM may fall by half, when using the climate data. When considering the free-floating carsharing service, and prediction for the short-term (i.e., 12 hours), the boosting algorithms (e.g. XGBoost, Catboost, and LightGBM) present superior performance, with less than 20% of mean absolute error when compared to the next best-ranked model (Prophet). On the other hand, Prophet performed better for predictions conducted on long-term periods.
Modaline sulfate promotes Oct4 expression and maintains self-renewal and pluripotency of stem cells through JAK/STAT3 and Wnt signaling pathways
Authors: Mei Xianglin , Zhao Hanhan , Ai Huihan , Wang Shuyue , Song Zhenbo , Zheng Lihua , Wang Guannan , Sun Ying , Bao Yongli
Published: August 2021

Background

Stem cells have been extensively explored for a variety of regenerative medical applications and they play an important role in clinical treatment of many diseases. However, the limited amount of stem cells and their tendency to undergo spontaneous differentiation upon extended propagation in vitro restrict their practical application. Octamer-binding transcription factor-4 (Oct4), a transcription factor belongs to the POU transcription factor family Class V, is fundamental for maintaining self-renewal ability and pluripotency of stem cells.

Methods

In the present study, we used the previously constructed luciferase reporters driven by the promoter and 3’-UTR of Oct4 respectively to screen potential activators of Oct4. Colony formation assay, sphere-forming ability assay, alkaline phosphatase (AP) activity assay and teratoma-formation assay were used to assess the role of modaline sulfate (MDLS) in promoting self-renewal and reinforcing pluripotency of P19 cells. Immunofluorescence, RT-PCR, and western blotting were used to measure expression changes of stem-related genes and activation of related signaling pathways.

Results

We screened 480 commercially available small-molecule compounds and discovered that MDLS greatly promoted the expression of Oct4 at both mRNA and protein levels. Moreover, MDLS significantly promoted the self-renewal capacity of P19 cells. Also, we observed that the expression of pluripotency markers and alkaline phosphatase (AP) increased significantly in MDLS-treated colonies. Furthermore, MDLS could promote teratoma formation and enhanced differentiation potential of P19 cells in vivo. In addition, we found that in the presence of LIF, MDLS could replace feeder cells to maintain the undifferentiated state of OG2-mES cells (Oct4-GFP reporter gene mouse embryonic stem cell line), and the MDLS-expanded OG2-mES cells showed an elevated expression levels of pluripotency markers in vitro. Finally, we found that MDLS promoted Oct4 expression by activating JAK/STAT3 and classic Wnt signaling pathways, and these effects were reversed by treatment with inhibitors of corresponding signaling pathways.

Conclusions

These findings demonstrated, for the first time, that MDLS could maintain self-renewal and pluripotency of stem cells.
FOXD1 promotes EMT and cell stemness of oral squamous cell carcinoma by transcriptional activation of SNAI2
Authors: Chen Yang , Liang Weilian , Liu Ke , Shang Zhengjun
Published: August 2021

Background

Epithelial-mesenchymal transition (EMT) and cell stemness are implicated in the initiation and progression of oral squamous cell carcinoma (OSCC). Revealing the intrinsic regulatory mechanism may provide effective therapeutic targets for OSCC.

Results

In this study, we found that Forkhead box D1 (FOXD1) was upregulated in OSCC compared with normal samples. Patients with a higher FOXD1 expression had a poorer overall survival and disease-free survival. Immunohistochemical staining results showed that FOXD1 expression was related to the clinical stage and relapse status of OSCC patients. When FOXD1 expression was knocked down in CAL27 and SCC25 cells, the migration, invasion, colony formation, sphere formation, and proliferation abilities decreased. Moreover, EMT and stemness-related markers changed remarkably, which indicated that the EMT process and cell stemness were inhibited. Conversely, overexpression of FOXD1 promoted EMT and cell stemness. Further study demonstrated that FOXD1 could bind to the promoter region and activate the transcription of SNAI2. In turn, the elevated SNAI2 affected EMT and cell stemness. An in vivo study showed that FOXD1-overexpressing CAL27 cells possessed a stronger tumorigenic ability.

Conclusions

Our findings revealed a novel mechanism in regulating EMT and cell stemness and proposed FOXD1 as a potential marker for the diagnosis and treatment of OSCC.
Management of proximal femur fractures in the elderly: current concepts and treatment options
Authors: Fischer H. , Maleitzke T. , Eder C. , Ahmad S. , Stöckle U. , Braun K. F.
Published: August 2021

As one of the leading causes of elderly patients’ hospitalisation, proximal femur fractures (PFFs) will present an increasing socioeconomic problem in the near future. This is a result of the demographic change that is expressed by the increasing proportion of elderly people in society. Peri-operative management must be handled attentively to avoid complications and decrease mortality rates. To deal with the exceptional needs of the elderly, the development of orthogeriatric centres to support orthogeriatric co-management is mandatory. Adequate pain medication, balanced fluid management, delirium prevention and the operative treatment choice based on comorbidities, individual demands and biological rather than chronological age, all deserve particular attention to improve patients’ outcomes. The operative management of intertrochanteric and subtrochanteric fractures favours intramedullary nailing. For femoral neck fractures, the Garden classification is used to differentiate between non-displaced and displaced fractures. Osteosynthesis is suitable for biologically young patients with non-dislocated fractures, whereas total hip arthroplasty and hemiarthroplasty are the main options for biologically old patients and displaced fractures. In bedridden patients, osteosynthesis might be an option to establish transferability from bed to chair and the restroom. Postoperatively, the patients benefit from early mobilisation and early geriatric care. During the COVID-19 pandemic, prolonged time until surgery and thus an increased rate of complications took a toll on frail patients with PFFs. This review aims to offer surgical guidelines for the treatment of PFFs in the elderly with a focus on pitfalls and challenges particularly relevant to frail patients.
The Swedish RAND-36: psychometric characteristics and reference data from the Mid-Swed Health Survey
Authors: Ohlsson-Nevo Emma , Hiyoshi Ayako , Norén Paulina , Möller Margareta , Karlsson Jan
Published: August 2021

Background

This study aims to evaluate data quality, scaling properties, and reliability of the Swedish RAND-36 in a general population sample and to present reference data for the Swedish population.

Methods

Testing of data quality, scaling assumptions and reliability followed methods recommended for the International Quality of Life Assessment Project, previously used for psychometric testing of SF-36 and RAND-36. Data were collected via regular mail for a random stratified sample of the general population in a Swedish county. Weighted means for RAND-36 scores were used and differences by sex, age, education, and occupational groups were tested.

Results

The response rate was 42%, and the sample comprised 3432 persons (45% men, 55% women) with a median age of 56.9 years. The internal consistency reliability was satisfactory, with Cronbach’s alphas > 0.80 for all eight scales. The percentage of missing items was low, ranging between 1.3% and 3.2%. No floor effects (≥15%) were noted, while ceiling effects were observed for physical functioning, role-functioning/physical, pain, role-functioning/emotional, and social functioning. Item–scale correlations were satisfactory (r ≥ 0.40). Correlations among the physical health scales were strong (range 0.58–0.68) as were the correlations among the mental health scales (range 0.58–0.73). Men reported significantly better health-related quality of life (HRQoL) on all scales, although the gender differences were small. Comparisons among age groups showed approximately equal scores among those 20–29, 30–39, and 40–49 years, while significant decreases in physical health were observed in the older age groups. Substantially worse physical health scores were observed in the oldest age group (80+). Significant differences among age groups were noted also for the mental health scales; however, better energy/fatigue and emotional well-being scores were seen in the older age groups, except for the oldest (80+). Those with university education reported significantly better scores on all scales compared to those with mandatory education.

Conclusions

The study suggests that the Swedish version of RAND-36 is an acceptable and reliable instrument for measuring HRQoL in the general population. The study provides reference data that can be used for norm-based comparisons.
Whistleblowing on photovoltaic operations in Nigeria: panacea for sustainable development
Authors: Okoro Ugochukwu K. , Chineke Theo Chidiezie
Published: August 2021

Background

There is no gainsaying about the importance of energy to the growth, development and socioeconomic well-being of any society. Photovoltaics (PV) have been identified not only as a means of meeting the energy needs of the Nigerian population but also as a tool in its national development. In this study, we reviewed the policy efforts of Nigeria in improving the renewable energy spread and the PV operations and utilization across the country.

Results

The technical audit of PV operations in Nigeria is evaluated using questionnaires administered in the 27 Local Government Areas in Imo State, as a case study. The component items in the latent variable scales of the audit have been tested for internal consistency using the Cronbach’s alpha. The good variable scale “Appropriateness for energy need” indicated a dissenting perception, whereas the acceptable variable scales “Adequacy in energy efficiency” and “Sustainability of PV project” indicated significant confidence in their perceptions. The perception in the energy need, which is associated with the limitations in PV utilization, is perceived as wrongdoings.

Conclusions

The whistleblowing policy is advocated as a germane measure to reduce or stop these wrongdoings and improve PV utilization and spread in Nigeria.
Effect of tourniquet application on cement penetration in primary total knee arthroplasty: a meta-analysis
Authors: Yao Shuxin , Zhang Weijie , Ma Jianbing , Wang Jianpeng
Published: August 2021

Background

Tourniquet application is expected to improve surgery exposure and cementation process in total knee arthroplasty (TKA) but its effectiveness remains controversial and needs to be further explored. The aim of this meta-analysis was to assess the effect of tourniquet in primary TKA. The hypothesis is that the tourniquet application affects the cement penetration in TKA.

Methods

A search was conducted in PubMed, Embase, and the Cochrane Library for the potentially eligible articles. Two independent researchers reviewed the articles retrieved against the pre-designed inclusion and exclusion criteria. In primary TKA, cement penetration was assessed, and the data between the tourniquet-assisted and non-tourniquet-assisted TKAs were compared. Statistical significance was set atP < 0.05.

Results

A total of 4 randomized controlled trials and 3 non-randomized controlled trials (involving 675 patients) were included. There was no significant difference between the tourniquet-assisted and non-tourniquet-assisted TKAs in terms of cement penetration (P > 0.05). There were no significant differences in the total surgical time, blood loss, blood transfusion, the Knee Society Score, and the visual analogue scale (VAS) between the two kinds of procedures (P > 0.05).

Conclusions

Tourniquet application may not affect cement penetration in primary TKA and may not help reduce blood loss, ease knee pain or improve the knee function. A surgeon may choose to use a tourniquet or not according to his or her own preference.

Level of Evidence

Level Ib, meta-analysis.
From spectral broadening to recompression: dynamics of incoherent optical waves propagating in the fiber
Authors: Ye Jun , Ma Xiaoya , Zhang Yang , Xu Jiangming , Zhang Hanwei , Yao Tianfu , Leng Jinyong , Zhou Pu
Published: August 2021

Interplay between dispersion and nonlinearity in optical fibers is a fundamental research topic of nonlinear fiber optics. Here we numerically and experimentally investigate an incoherent continuous-wave (CW) optical field propagating in the fiber with normal dispersion, and introduce a distinctive spectral evolution that differs from the previous reports with coherent mode-locked fiber lasers and partially coherent Raman fiber lasers [Nat. Photonics 9, 608 (2015).]. We further reveal that the underlying physical mechanism is attributed to a novel interplay between group-velocity dispersion (GVD), self-phase modulation (SPM) and inverse four-wave mixing (IFWM), in which SPM and GVD are responsible for the first spectral broadening, while the following spectral recompression is due to the GVD-assisted IFWM, and the eventual stationary spectrum is owing to the dominant contribution of GVD effect. We believe this work can not only expand the light propagation in the fiber to a more general case and help advance the physical understanding of light propagation with different statistical properties, but also benefit the applications in sensing, telecommunications and fiber lasers.
Time-lapse borehole gravity imaging of CO2 injection and withdrawal in a closed carbonate reef
Authors: Bonneville Alain , Black Andrew J. , Hare Jennifer L. , Kelley Mark E. , Place Matthew , Gupta Neeraj
Published: August 2021

Three borehole gravity (BHG) surveys were performed in 2013, 2016, and 2018 to monitor the changes in gravity/density as a result of the injection and withdrawal of carbon dioxide ([Formula: see text]) into and out of the Dover 33 carbonate reservoir reef in Northern Michigan. The observed gravity changes and inferred density changes have been modeled to determine the flow and storage zones of the injected [Formula: see text] in the reef. The high quality and low level of uncertainty of the data collected make them useful for delineating the [Formula: see text] plume position over time and for identifying the oil sweeping extent and mechanisms in the Dover 33 reef. The time-lapse gravity results indicate the effects of the changing [Formula: see text] mass within the reservoir, consistent with increasing mass from 2013 to 2016 (following [Formula: see text] injection) and a decreasing mass from 2016 to 2018 (after [Formula: see text] withdrawal). Three-dimensional imaging of fluid migrations in the reef has been obtained by coupling the time-lapse BHG results to a 3D porosity and permeability model. This coupled approach allows the evaluation of the volume of the reef affected by the injection of [Formula: see text] between 2013 and 2016, the efficiency of the oil sweeping between 2016 and 2018, and the location of the residual [Formula: see text] plume in the reef after 2018.
Adaptive 27-point finite-difference frequency-domain method for wave simulation of 3D acoustic wave equation
Authors: Xu Wenhao , Wu Bangyu , Zhong Yang , Gao Jinghuai , Liu Qing Huo
Published: August 2021

The finite-difference frequency-domain (FDFD) method has important applications in the wave simulation of various wave equations. To promote the accuracy and efficiency for wave simulation with the FDFD method, we have developed a new 27-point FDFD stencil for 3D acoustic wave equations. In the developed stencil, the FDFD coefficients depend not only on the ratios of cell sizes in the x-, y-, and z-directions but also depend on the spatial sampling density (SD) in terms of the number of wavelengths per grid. The corresponding FDFD coefficients can be determined efficiently by making use of the plane-wave expression and the lookup table technique. We also develop a new way for designing an adaptive FDFD stencil by directly adding some correction terms to the conventional second-order FDFD stencil, which is simpler to use and easier to generalize. Corresponding dispersion analysis indicates that, compared to the optimal 27-point stencil derived from the average-derivative method (ADM), the developed adaptive 27-point stencil can reduce the required SD from approximately 4 to 2.2 points per wavelength (PPW) for a cubic mesh and to 2.7 PPW for a general cuboid mesh. Numerical examples of a 3D homogeneous model and SEG/EAGE salt-dome model indicate that the developed stencil is more accurate than the ADM 27-point stencil for cubic and general cuboid meshes, while requiring similar CPU time and computational memory as the ADM 27-point stencil for direct and iterative solvers.
Prenatal Androgen Exposure Alters KNDy Neurons and Their Afferent Network in a Model of Polycystic Ovarian Syndrome
Authors: Moore Aleisha M , Lohr Dayanara B , Coolen Lique M , Lehman Michael N
Published: August 2021

Polycystic ovarian syndrome (PCOS), the most common endocrinopathy affecting women worldwide, is characterized by elevated luteinizing hormone (LH) pulse frequency due to the impaired suppression of gonadotrophin-releasing hormone (GnRH) release by steroid hormone negative feedback. Although neurons that co-express kisspeptin, neurokinin B, and dynorphin (KNDy cells) were recently defined as the GnRH/LH pulse generator, little is understood about their role in the pathogenesis of PCOS. We used a prenatal androgen-treated (PNA) mouse model of PCOS to determine whether changes in KNDy neurons or their afferent network underlie altered negative feedback. First, we identified elevated androgen receptor gene expression in KNDy cells of PNA mice, whereas progesterone receptor and dynorphin gene expression was significantly reduced, suggesting elevated androgens in PCOS disrupt progesterone negative feedback via direct actions upon KNDy cells. Second, we discovered GABAergic and glutamatergic synaptic input to KNDy neurons was reduced in PNA mice. Retrograde monosynaptic tract-tracing revealed a dramatic reduction in input originates from sexually dimorphic afferents in the preoptic area, anteroventral periventricular nucleus, anterior hypothalamic area and lateral hypothalamus. These results reveal 2 sites of neuronal alterations potentially responsible for defects in negative feedback in PCOS: changes in gene expression within KNDy neurons, and changes in synaptic inputs from steroid hormone-responsive hypothalamic regions. How each of these changes contribute to the neuroendocrine phenotype seen in in PCOS, and the role of specific sets of upstream KNDy afferents in the process, remains to be determined.
Phosphorylated cingulin localises GEF-H1 at tight junctions to protect vascular barriers in blood endothelial cells
Authors: Holzner Silvio , Bromberger Sophie , Wenzina Judith , Neumüller Karin , Holper Tina-Maria , Petzelbauer Peter , Bauer Wolfgang , Weber Benedikt , Schossleitner Klaudia
Published: August 2021

Dysfunction of vascular barriers is a critical step in inflammatory diseases. Endothelial tight junctions (TJs) control barrier function, and the cytoplasmic adaptor protein cingulin connects TJs to signalling pathways. However, local events at TJs during inflammation are largely unknown. In this study, we investigate the local response of TJ adaptor protein cingulin and its interaction with Rho guanine nucleotide exchange factor H1 (GEF-H1, also known as ARHGEF2) upon vascular barrier disruption to find a new approach to counteract vascular leak. Based on transendothelial-electrical-resistance (TEER) measurements, cingulin strengthened barrier integrity upon stimulation with histamine, thrombin and VEGF. Cingulin also attenuated myosin light chain 2 (MLC2; also known as MYL2) phosphorylation by localising GEF-H1 to cell junctions. By using cingulin phosphomutants, we verified that the phosphorylation of the cingulin head domain is required for its protective effect. Increased colocalisation of GEF-H1 and cingulin was observed in the vessels of vasculitis patients compared to those in healthy skin. Our findings demonstrate that cingulin can counteract vascular leak at TJs, suggesting the existence of a novel mechanism in blood endothelial cells that protects barrier function during disease.
New species of Diaphera Albers, 1850 (Gastropoda: Pulmonata: Streptaxidae) from Kalimantan, Borneo (Indonesia)
Authors: Vermeulen Jaap J.
Published: August 2021

Eight new species and one new subspecies of the genus Diaphera (Streptaxidae) are described: D. amphoreomorpha, D. crenata, D. kionion, D. striata, D. auriculata, D. crassa, D. rhysauchen rhysauchen, D. rhysauchen percostata, and D. sororcula. All species originate from Kalimantan, the Indonesian part of the island of Borneo.
High-risk human-caused pathogen exposure events from 1975-2016
Authors: Manheim David , Lewis Gregory
Published: August 2021

Biological agents and infectious pathogens have the potential to cause very significant harm, as the natural occurrence of disease and pandemics makes clear. As a way to better understand the risk of Global Catastrophic Biological Risks due to human activities, rather than natural sources, this paper reports on a dataset of 71 incidents involving either accidental or purposeful exposure to, or infection by, a highly infectious pathogenic agent.

There has been significant effort put into both reducing the risk of purposeful spread of biological weapons, and biosafety intended to prevent the exposure to, or release of, dangerous pathogens in the course of research. Despite these efforts, there are incidents of various types that could potentially be controlled or eliminated by different lab and/or bioweapon research choices and safety procedures.

The dataset of events presented here was compiled during a project conducted in 2019 to better understand biological risks from anthropic sources.

The events which are listed are unrelated to clinical treatment of naturally occurring outbreaks, and are instead entirely the result of human decisions and mistakes. While the events cover a wide range of cases, the criteria used covers a variety of events previously scattered across academic, policy, and other unpublished or not generally available sources.
Reverse transcription PCR to detect low density malaria infections
Authors: Christensen Peter , Bozdech Zbynek , Watthanaworawit Wanitda , Rénia Laurent , Malleret Benoît , Ling Clare , Nosten François
Published: August 2021

Background: Targeted malaria elimination strategies require highly sensitive tests to detect low density malaria infections (LDMI). Commonly used methods for malaria diagnosis such as light microscopy and antigen-based rapid diagnostic tests (RDTs) are not sensitive enough for reliable identification of infections with parasitaemia below 200 parasites per milliliter of blood. While targeted malaria elimination efforts on the Thailand-Myanmar border have successfully used high sample volume ultrasensitive quantitative PCR (uPCR) to determine malaria prevalence, the necessity for venous collection and processing of large quantities of patient blood limits the widespread tractability of this method.

Methods: Here we evaluated a real-time reverse transcription PCR (RT-qPCR) method that reduces the required sample volume compared to uPCR. To do this, 304 samples collected from an active case detection program in Kayin state, Myanmar were compared using uPCR and RT-qPCR.

Results: Plasmodium spp. RT-qPCR confirmed 18 of 21 uPCR Plasmodium falciparum positives, while P. falciparum specific RT-qPCR confirmed 17 of the 21 uPCR P. falciparum positives. Combining both RT-qPCR results increased the sensitivity to 100% and specificity was 95.1%.

Conclusion: Malaria detection in areas of low transmission and LDMI can benefit from the increased sensitivity of ribosomal RNA detection by RT-PCR, especially where sample volume is limited. Isolation of high quality RNA also allows for downstream analysis of malaria transcripts.