bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Kinect-Enhanced Lymphatic Exercise Intervention on Lymphatic Pain, Swelling, and Lymph Fluid Level
Authors: Fu Mei R. , McTernan Melissa L. , Qiu Jeanna M. , Ko Eunjung , Yazicioglu Simay , Axelrod Deborah , Guth Amber , Fan Zhipeng , Sang Anna , Miaskowski Christine , Wang Yao
Published: June 2021

Background:

The-Optimal-Lymph-Flow (TOLF) intervention aims to promote lymph flow through therapeutic lymphatic exercises to relieve lymphatic pain, swelling, lymphedema symptoms, and to decrease lymph fluid levels among breast cancer survivors. To enhance the efficacy of the TOLF intervention, an innovative, intelligent, Kinect-enhanced lymphatic exercise intervention (Kinect-TOLF) was developed to teach patients to perform the lymphatic exercises correctly.

Objectives:

This feasibility trial aimed to determine the feasibility, usability, and effects of the Kinect-TOLF on lymphatic pain, swelling, lymphedema symptoms, and lymph fluid levels.

Methods:

A single-arm feasibility trial with a pre- and post-test design was employed to recruit 30 breast cancer survivors with persistent lymphatic pain or swelling. Patients received a single training session to learn how to perform the lymphatic exercises using the Kinect-TOLF program. Descriptive statistics, Wilcoxon signed-rank tests, t-test, Spearman’s rank correlation coefficients, linear regressions, and Cohen’s d were performed for data analysis. Qualitative data were assessed for common themes.

Results:

The Kinect-TOLF was effective in training patients to perform the lymphatic exercises correctly with high user satisfaction. Significant reductions were found in scores of lymphatic pain ( MedΔ = −1.00, CI  = [−1.5, −0.1], P = .004), arm/hand swelling ( MedΔ = −1.00, CI = [−1.5, −0.5], P = .004), total swelling ( MedΔ = −1.5, CI = [−2.0, −1.0], P = .003), number of lymphedema symptoms ( MΔ = −3.8, CI = [−5.5, −2.1], P < .001), and lymphedema symptom severity ( MΔ = −5.3, CI = [−9.5, −1.1], P = .016). A significant reduction in lymph fluid levels was found in mean L-Dex scores ( MΔ = −2.68, CI = [−4.67, −0.69], P = .010). Greater decrease in mean L-Dex scores were found in patients with abnormal lymph fluid levels (L-Dex ≥ 7.1) ( MΔ = −5.19, CI = [−1.75, −8.63], P = .008). Patients’ qualitative feedback supported the results of the study.

Conclusions:

The Kinect-TOLF is safe, feasible, and effective in reducing lymphatic pain, swelling, lymphedema symptoms, and in decreasing lymph fluid levels. Future research should focus on a randomized clinical trial to confirm the unique or synergistic efficacy of the Kinect-TOLF in comparison with current lymphedema treatment and other forms of exercises or movement therapy. This study was registered in ClinicalTrials.gov with US ClinicalTrials.gov Identifier: NCT03999177.
From the Train Yard to the Auction House: Connecting the Graffiti Subculture to the Art Market
Authors: Weill Pierre-Edouard
Published: June 2021

Various cultural intermediaries have become involved in connecting graffiti writing to the art market. Through this case study, I shed light on the division of intermediation labour in the commercialization process of artworks stemming from subcultures in a global art market. Since the early 1970s, an international network of cultural brokers has gradually been set up in a frontier zone between art collectors and graffiti writers. Interviews, documentary sources and participative observation as an insider made it possible to identify these intermediaries and their specific roles and resources. My investigation sheds light on three historical phases of intermediation: from the first initiatives in New York in the 1970s to thematic auctions in French between 2006 and 2017. The first two phases ended in commercial and critical failure, first in American galleries and then in European museums, but the third phase led to economic success on the secondary art market, followed by public institutions’ validation. Three types of intermediaries are distinguished: commissioned experts from graffiti subculture, who select and encourage graffiti writers to produce marketable works; entrepreneurs, who seek to create a niche in the art market and promote a flattering image of graffiti art collectors, a group to which they often also belong; established auctioneers, who mobilize influential art buyers and encourage their favourable reception of graffiti artworks in order to expand their business. Whether they collaborate or compete with each other, these cultural intermediaries have complementary roles and resources linked to their social trajectories. However, they reap unequal benefits from their activities, whose impact on subcultural practices is finally discussed.
Ten-year survival analysis of patients with primary Sjögren’s syndrome in China: a national prospective cohort study
Authors: Qian Junyan , He Chengmei , Li Ya , Peng Linyi , Yang Yunjiao , Xu Dong , Fei Yunyun , Zhang Wen , Zhao Yan , Dong Yi , Li Yongzhe , Zhang Xuan , Chen Hua , Yang Yanlei , Chen Zhilei , Liu Suying , Wang Li , Zhang Fengchun
Published: June 2021

Aims:

To investigate the long-term survival of patients with primary Sjögren’s syndrome (pSS) in China.

Methods:

Patients with pSS who fulfilled the 2002 American–European Consensus Group classification criteria were prospectively enrolled from 2004 to 2011. Their baseline clinical, laboratory, and therapeutic data were collected. The primary endpoint was all-cause death by January 2018. The standard mortality ratio (SMR) was calculated by comparing with age-matched and sex-matched mortality data of the general population. Kaplan–Meier curves were obtained by time-to-event analysis. Univariate and multivariate Cox hazards regression analyses were performed to identify risk factors for mortality.

Results:

A total of 1054 patients were enrolled and 834 patients were followed up for a median of 94.8 months, with 48 confirmed deaths. The total SMR was 3.63 [95% confidence interval (CI) 2.60–4.66]. The 3-, 5-, and 10-year survival rates were 98.4%, 97.5%, and 92.9%, respectively. Infection, malignancy, and respiratory failure were the top three causes of mortality. We identified male sex [hazard ratio (HR) = 3.00, 95% CI 1.23–7.31], age at diagnosis ⩾50 years of age (HR = 7.69, 95% CI 3.01–19.62), thrombocytopenia (HR = 1.93, 95% CI 1.01–3.72), and interstitial lung disease (HR = 5.96, 95% CI 2.24–15.82) as the independent prognostic factors of death.

Conclusions:

The mortality rates of Chinese patients with pSS are higher than those of the general population. Male patients of elder age at diagnosis complicated with thrombocytopenia and interstitial lung disease might be suggestive for poorer survival and require closer follow up.
Effective management of advanced colon cancer genotyping microsatellite stable/microsatellite instable-low with Kirsten rat sarcoma viral oncogene mutation using nivolumab plus ipilimumab combined with regorafenib and irinotecan: A case report
Authors: Cui Yingqiang , Ou Yimeng , Luo Yongping , Yu Jiongbiao , Lin Yiguang , Chen Size
Published: June 2021

Microsatellite stable /microsatellite instable-low is the most common colorectal cancer genotype, counting for approximately 85% of common colorectal cancer patients. Treatment of advanced microsatellite stable/microsatellite instable-low colorectal cancer is difficult and successful pharmacological treatment options are currently lacking. Here, we report a case of a 37-year-old man with advanced colorectal cancer genotyping microsatellite stable/microsatellite instable-low with a Kirsten rat sarcoma viral oncogene (G12V) mutation. Following palliative surgery, the patient did not response to the common recommended chemotherapy FOLFIRI regimen and other chemotherapy options. Finally, the patient was successfully treated using a unique combinational immunotherapy, using nivolumab plus ipilimumab combined with regorafenib and irinotecan. Significant improvement in the Karnofsky Performance Status scores, liver function and well-being, reduction in serum tumor biomarkers, and reduction in the size of multiple liver metastatic tumors was evident. This report provides a rare case in which a unique and effective combinational immunotherapy for refractory advanced colon cancer patients is discussed. It encourages further research into combined immunotherapy for immuno-insensitive colon cancer patients.
Sleep quality in the chronic stage of concussion is associated with poorer recovery: A systematic review
Authors: Ludwig Rebecca , Nelson Eryen , Vaduvathiriyan Prasanna , Rippee Michael A , Siengsukon Catherine
Published: June 2021

Background

Recovery from a concussion varies based on a multitude of factors. One such factor is sleep disturbances. In our prior review, it was observed that in the acute phase, sleep disturbances are predictive of poor outcomes following a concussion. The literature gap remains on how sleep in the chronic phase of recovery affects outcomes.

Objective

To examine the association between sleep quality during the chronic stage of concussion and post-concussion outcomes. Literature Survey: Literature searches were performed during 1 July to 1 August 2019 in selected databases along with searching grey literature. Out of the 733 results, 702 references were reviewed after duplicate removal.

Methods

Three reviewers independently reviewed and consented on abstracts meeting eligibility criteria ( n = 35). The full-text articles were assessed independently by two reviewers. Consensus was achieved, leaving four articles. Relevant data from each study was extracted using a standard data-extraction table. Quality appraisal was conducted to assess potential bias and the quality of articles.

Results

One study included children (18–60 months) and three studies included adolescents and/or adults (ranging 12–35 years). The association between sleep and cognition (two studies), physical activity (one study), and emotion symptoms (one study) was examined. Sleep quality was associated with decreased cognition and emotional symptoms, but not with meeting physical activity guidelines six months post-concussion injury.

Conclusions

The heterogeneity in age of participants and outcomes across studies and limited number of included studies made interpretations difficult. Future studies may consider if addressing sleep quality following concussion will improve outcomes.
Sibling Alcohol Use Disorder Is Associated With Increased Risk for Suicide Attempt
Authors: Stephenson Mallory E. , Larsson Lönn Sara , Salvatore Jessica E. , Sundquist Jan , Kendler Kenneth S. , Sundquist Kristina , Edwards Alexis C.
Published: June 2021

The association between having a sibling diagnosed with alcohol use disorder (AUD) and risk for suicide attempt may be attributable to shared genetic liability between AUD and suicidal behavior, effects of environmental exposure to a sibling’s AUD, or both. To distinguish between these alternatives, we conducted a series of Cox regression models using data derived from Swedish population-based registers with national coverage. Among full sibling pairs (656,807 males and 607,096 females), we found that, even after we accounted for the proband’s AUD status, the proband’s risk for suicide attempt was significantly elevated when the proband’s sibling was affected by AUD. Furthermore, the proband’s risk for suicide attempt was consistently higher when the sibling’s AUD registration had occurred more recently. Our findings provide evidence for exposure to sibling AUD as an environmental risk factor for suicide attempt and suggest that clinical outreach may be warranted following a sibling’s diagnosis with AUD.
Multidisciplinary Practice Variations of Anti-Thrombotic Strategies for Free Tissue Transfers
Authors: Huynh Minh N. Q. , Bhagirath Vinai , Gupta Michael , Avram Ronen , Cheung Kevin
Published: June 2021

Background: Venous thrombosis, the leading cause of free flap failure, may have devastating consequences. Many anti-thrombotic agents and protocols have been described for prophylaxis and treatment of venous thrombosis in free flaps. Methods: National surveys were distributed to microsurgeons (of both Plastics and ENT training) and hematology and thrombosis specialists. Data were collected on routine screening practices, perceived risk factors for flap failure, and pre-, intra-, and post-operative anti-thrombotic strategies. Results: There were 722 surveys distributed with 132 (18%) respondents, consisting of 102 surgeons and 30 hematologists. Sixty-five surgeons and 9 hematologists routinely performed or managed patients with free flaps. The top 3 perceived risk factors for flap failure according to surgeons were medical co-morbidities, past arterial thrombosis, and thrombophilia. Hematologists, however, reported diabetes, smoking, and medical co-morbidities as the most important risk factors. Fifty-four percent of physicians routinely used unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) as a preoperative agent. Surgeons routinely flushed the flap with heparin (37%), used UFH IV (6%), or both (8%) intra-operatively. Surgeons used a range of post-operative agents such as UFH, LMWH, aspirin, and dextran while hematologists preferred LMWH. There was variation of management strategies if flap thrombosis occurred. Different strategies consisted of changing recipient vessels, UFH IV, flushing the flap, adding post-operative agents, or a combination of strategies. Conclusions: There are diverse practice variations in anti-thrombotic strategies for free tissue transfers and a difference in perceived risk factors for flap failure that may affect patient management.
Patient‐Reported Pain and Opioid Use After Ambulatory Head and Neck Surgery
Authors: Cheng Michael Z. , Kim Matthew , Sclafani Anthony P. , Kjaer Klaus , Kutler David Ivan
Published: June 2021

Objective

The main objective of this study was to quantify daily pain and opioid use in patients after hemithyroidectomy and cervical lymph node biopsy (CLNB). The secondary objective was to identify factors associated with decreased pain and opioid use.

Study Design

Prospective cohort study from June 2017 to February 2019. Patients were given paper surveys to record daily postoperative opioid use and maximal pain on a visual analog scale.

Setting

Single institution (NewYork‐Presbyterian/Weill Cornell Medical Center).

Methods

All adult patients undergoing hemithyroidectomy and CLNB by a single surgeon were consecutively selected for participation. Patients recorded daily pain and opioid analgesic use over a 2‐week postoperative period.

Results

Of 33 patients enrolled, 29 (87.9%) returned a survey. Thirteen underwent CLNB, and 16 underwent hemithyroidectomy. Pain resolved after both procedures by the end of the 2‐week period. CLNB patients used a median (interquartile range) of 15.0 (0‐41.2) morphine milligram equivalents (MME), and 95% used 70 or fewer MME. Hemithyroidectomy patients used a median of 8.2 (4.5‐13.9) MME, and 95% used 30 or fewer MME. Use of nonopioid analgesics was associated with a statistically significant decrease in pain (56.1 vs 171 visual analog scale, 95% confidence interval [CI] of Δ = [12.0 to 217.8]) and opioid use (12.2 vs 48.8 MME, 95% CI of Δ = [5.0 to 68.1 MME]) in CLNB but not in hemithyroidectomy.

Conclusion

Patients have low pain and opioid requirements after hemithyroidectomy and CLNB. Head and neck surgeons should evaluate their opioid‐prescribing patterns for opportunities to safely decrease postoperative prescriptions.
Improving adherence in chronic airways disease: are we doing it wrongly?
Authors: d'Ancona Gráinne , Weinman John
Published: June 2021

Non-adherence to medicines is a significant clinical and financial burden, but successful strategies to improve it, and thus bring about significant improvements in clinical outcome, remain elusive. Many barriers exist, including a lack of awareness amongst some healthcare professionals as to the extent and impact of non-adherence and a dearth of skills to address it successfully. Patients may not appreciate that they are non-adherent, feel they cannot disclose it or underestimate its impact on their health in the short and longer term. In describing the evidence-based frameworks that identify the causal factors behind medicines taking (or not taking) behaviours, we can start to personalise interventions to enable individuals to make informed decisions about their treatments and thus overcome real and perceived barriers to adherence.

Educational aims

To understand the underlying principles of why a patient may or may not take medicines as agreed.

To choose targeted interventions to support better adherence.
Predicting antifreeze proteins with weighted generalized dipeptide composition and multi-regression feature selection ensemble
Authors: Wang Shunfang , Deng Lin , Xia Xinnan , Cao Zicheng , Fei Yu
Published: June 2021

Background

Antifreeze proteins (AFPs) are a group of proteins that inhibit body fluids from growing to ice crystals and thus improve biological antifreeze ability. It is vital to the survival of living organisms in extremely cold environments. However, little research is performed on sequences feature extraction and selection for antifreeze proteins classification in the structure and function prediction, which is of great significance.

Results

In this paper, to predict the antifreeze proteins, a feature representation of weighted generalized dipeptide composition (W-GDipC) and an ensemble feature selection based on two-stage and multi-regression method (LRMR-Ri) are proposed. Specifically, four feature selection algorithms: Lasso regression, Ridge regression, Maximal information coefficient and Relief are used to select the feature sets, respectively, which is the first stage of LRMR-Ri method. If there exists a common feature subset among the above four sets, it is the optimal subset; otherwise we use Ridge regression to select the optimal subset from the public set pooled by the four sets, which is the second stage of LRMR-Ri. The LRMR-Ri method combined with W-GDipC was performed both on the antifreeze proteins dataset (binary classification), and on the membrane protein dataset (multiple classification). Experimental results show that this method has good performance in support vector machine (SVM), decision tree (DT) and stochastic gradient descent (SGD). The values of ACC, RE and MCC of LRMR-Ri and W-GDipC with antifreeze proteins dataset and SVM classifier have reached as high as 95.56%, 97.06% and 0.9105, respectively, much higher than those of each single method: Lasso, Ridge, Mic and Relief, nearly 13% higher than single Lasso for ACC.

Conclusion

The experimental results show that the proposed LRMR-Ri and W-GDipC method can significantly improve the accuracy of antifreeze proteins prediction compared with other similar single feature methods. In addition, our method has also achieved good results in the classification and prediction of membrane proteins, which verifies its widely reliability to a certain extent.
RNA sequencing reveals transcriptomic changes in tobacco (Nicotiana tabacum) following NtCPS2 knockdown
Authors: He Lingxiao , Liu Huabing , Cheng Changhe , Xu Min , He Lei , Li Lihua , Yao Jian , Zhang Wenjun , Zhai Zhengguang , Luo Qinzhan , Sun Jutao , Yang Tiezhao , Xu Shixiao
Published: June 2021

Background

Amber-like compounds form in tobacco (Nicotiana tabacum) during leaf curing and impact aromatic quality. In particular, cis-abienol, a polycyclic labdane-related diterpenoid, is of research interest as a precursor of these compounds. Glandular trichome cells specifically express copalyl diphosphate synthase (NtCPS2) at high levels in tobacco, which, together with NtABS, are major regulators of cis-abienol biosynthesis in tobacco.

Results

To identify the genes involved in the biosynthesis of cis-abienol in tobacco, we constructed transgenic tobacco lines based on an NtCPS2 gene-knockdown model using CRISPR/Cas9 genome-editing technology to inhibit NtCPS2 function in vitro. In mutant plants, cis-abienol and labdene diol contents decreased, whereas the gibberellin and abscisic acid (ABA) contents increased compared with those in wild-type tobacco plants. RNA sequencing analysis revealed the presence of 9514 differentially expressed genes (DEGs; 4279 upregulated, 5235 downregulated) when the leaves of wild-type and NtCPS2-knockdown tobacco plants were screened. Among these DEGs, the genes encoding cis-abienol synthase, ent-kaurene oxidase, auxin/ABA-related proteins, and transcription factors were found to be involved in various biological and physiochemical processes, including diterpenoid biosynthesis, plant hormone signal transduction, and plant-pathogen interactions.

Conclusions

The present study provides insight into the unique transcriptome profile of NtCPS2 knockdown tobacco, allowing for a better understanding of the biosynthesis of cis-abienol in tobacco.
Effects of head positions on awake fiberoptic bronchoscope oral intubation: a randomized controlled trial
Authors: Liu Zhuo , Zhao Li , Ma Zhongfeng , Liu Meiqi , Qi Xiaohang , Jia Qianqian , Liang Shujuan , Yang Xiaochun
Published: June 2021

Background

There are many factors affecting the success rate of awake orotracheal intubation via fiberoptic bronchoscope. We performed this study was to investigate the effects of head positions on awake Fiberoptic bronchoscope oral intubation.

Methods

Seventy-five adult patients, received general anaesthesia were included in this study. After written informed consent, these patients were undergoing awake orotracheal intubation via fiberoptic-bronchoscope and according to the head position, the patients were randomized allocated to neutral position group (NP group), sniffing position group (SP group) or extension position group (EP group). After sedation the patients were intubated by an experienced anesthesiologist. The time to view the vocal cords, the percentage of glottic opening scores (POGO), the time to insert the tracheal tube into trachea and the visual analog scale (VAS) scores for ease experienced of passing the tracheal tube through glottis, the hemodynamic changes and the adverse events after surgery were recorded.

Results

The time to view the vocal cords was significantly shorter and the POGO scores was significantly higher in the EP group compared with the other two groups (P < 0.05); The SpO2 in the EP group was higher than NP group at before intubation and higher than SP group and NP group at immediate after intubation (P < 0.05); The time to insert the tracheal tube into trachea, the VAS scores for passing the tracheal tube through glottis, the coughing scores had no significant differences among groups (P > 0.05). There were also no significant differences regard to the incidence of postoperative complications, mean arterial pressure and heart rate among the groups (P > 0.05).

Conclusions

The head at extension position had a best view of glottic opening than neutral position or sniffing position during awake Fiberoptic bronchoscope oral intubation, so extension position was recommended as the starting head position for awake Fiberoptic bronchoscope oral intubation.

Trial registration

Clinical Trials.gov. no. NCT02792855. Registered at https://register.clinicaltrials.gov on 23 september 2017.
Evaluation of different DNA extraction methods and loop-mediated isothermal amplification primers for the detection of Mycobacterium ulcerans in clinical specimens
Authors: Ablordey Anthony , Ahotor Evans , Narh Charles A. , King Sandra A. , Cruz Isra , Ndung’u Joseph M. , de Souza Dziedzom K.
Published: June 2021

Background

Early diagnosis and treatment of Buruli ulcer is critical in order to avoid the debilitating effects of the disease. In this regard, the development of new diagnostic and point of care tools is encouraged. The loop-mediated isothermal amplification for the detection of Mycobacterium ulcerans represents one of the new tools with a good potential of being developed into a point of care test. There is however the need to standardize the assays, reduce sample preparation times, improve the detection/visualization system and optimize them for high-throughput screening, adaptable to low resourced laboratories.

Methods

In this study, we assessed two DNA extraction protocols (modified Boom and EasyNAT methods), three previously published LAMP primer sets (BURULI, MU 2404 and BU-LAMP), and compared the sensitivity and specificity of LAMP assays on three DNA amplification platforms.

Results

Our results show that Buruli ulcer diagnosis using primers targeting IS2404 for the LAMP method is sensitive (73.75–91.49%), depending on the DNA extraction method used. Even though the modified Boom DNA extraction method provided the best results, its instrumentation requirement prevent it from being field applicable. The EasyNAT method on the other hand is simpler and may represent the best method for DNA extraction in less resourced settings.

Conclusions

For further work on the development and use of LAMP tests for Buruli diagnosis, it is recommended that the BURULI sets of primers be used, as these yielded the best results in terms of sensitivity (87.50–91.49%) and specificity (89.23–100%), depending on the DNA extraction methods used.
Clinical features and development of Sepsis in Klebsiella pneumoniae infected liver abscess patients: a retrospective analysis of 135 cases
Authors: Li Shixiao , Yu Sufei , Peng Minfei , Qin Jiajia , Xu Chunyan , Qian Jiao , He Minmin , Zhou Peng
Published: June 2021

Background

Klebsiella pneumoniae is a primary pathogen of pyogenic liver abscess (PLA). However, little data are available on combination with sepsis. In this study, we aimed to evaluate the clinical characteristics and prognostic differences of PLA patients with sepsis.

Methods

This retrospective cohort study was conducted to investigate 135 patients with confirmed Klebsiella pneumoniae-caused liver abscesses (KPLA) from a tertiary teaching hospital, from 2013 to 2019. The patients were divided into two groups, KPLA with sepsis and KPLA without sepsis. The demographic characteristics, clinical features as well as laboratory and microbiologic findings were analyzed.

Results

A total of 135 patients with KPLA were analyzed. The mean age of patients was 60.9 ± 12.7 years, and the percentage of men was 59.3%. Among them, 37/135 (27.4%) of patients had sepsis and the mortality rate was 1.5%. The most common symptom was fever (91.1%). KPLA patients with sepsis had a significantly higher proportion of frailty, diarrhea, fatty liver, chronic renal insufficiency, and hepatic dysfunction compared to KPLA patients without sepsis (p < 0.05). Antibiotic therapy and percutaneous drainage were most frequently therapeutic strategy. Furthermore, the incidences of sepsis shock and acute respiratory distress syndrome were higher in the sepsis group compared to the non-sepsis group. As for metastatic infections, the lung was the most common site. In addition, KPLA patients with sepsis showed respiratory symptoms in 11 patients, endophthalmitis in 4 patients, and meningitis in 1 patient.

Conclusion

Our findings emphasize that KPLA patients combined with or without sepsis have different clinical features, but KPLA patients with sepsis have higher rates of complications and metastatic infections. Taken together, further surveillance and control of septic spread is essential for KPLA patients.
Development of a preliminary conceptual model of the patient experience of chronic kidney disease: a targeted literature review and analysis
Authors: Flythe Jennifer E. , Karlsson Niklas , Sundgren Anna , Cordero Paul , Grandinetti Amanda , Cremisi Henry , Rydén Anna
Published: June 2021

Background

Patient-reported outcome (PRO) instruments should capture the experiences of disease and treatment that patients consider most important in order to inform patient-centred care and product development. The aim of this study was to develop a preliminary conceptual model of patient experience in chronic kidney disease (CKD) based on a targeted literature review and to characterize existing PRO instruments used in CKD.

Methods

PubMed, EMBASE and Cochrane databases and recent society meetings were searched for publications reporting signs/symptoms and life impacts of CKD. Concepts identified in the literature review were used to develop a preliminary conceptual model of patient experience of CKD, overall, and within patient subpopulations of differing CKD causes, severities and complications. PRO instruments, identified from PRO databases, CKD literature and CKD clinical trials, were assessed for content validity, psychometric strength and coverage of concepts in the literature review.

Results

In total, 100 publications met criteria for analysis; 56 signs/symptoms and 37 life impacts of CKD were identified from these sources. The most frequently mentioned signs/symptoms were pain/discomfort (57% of publications) and tiredness/low energy/lethargy/fatigue (42%); the most commonly reported life impacts were anxiety/depression (49%) and decrements in physical functioning (43%). Signs/symptoms and life impacts varied across the subpopulations and were more frequent at advanced CKD stages. The preliminary conceptual model grouped signs/symptoms into seven domains (pain/discomfort; energy/fatigue; sleep-related; gastrointestinal-related; urinary-related; skin−/hair−/nails-related; and other) and life impacts into six domains (psychological/emotional strain; cognitive impairment; dietary habit disruption; physical function decrements; interference with social relationships; and other). Eleven PRO instruments were considered to be promising for use in CKD; all had limitations.

Conclusions

Although preliminary, the proposed conceptual model highlights key PROs for people with CKD and is intended to spur development of more tailored PRO instruments to assess these concepts.
The impact of COVID-19 pandemic on the health-seeking behaviour of an Asian population with acute respiratory infections in a densely populated community
Authors: Tan Hwee Mian Jane , Tan Mui Suan , Chang Zi Ying , Tan Kee Tung , Ee Guan Liang Adrian , Ng Chee Chin David , Hwang Ying Khee William , Koh Yi Ling Eileen , Low Yan Ping Sarah , Tan Ngiap Chuan
Published: June 2021

Background

The COVID-19 pandemic led to the implementation of various non-pharmaceutical interventions (NPI) as the Singapore government escalated containment efforts from DORSCON Orange to Circuit Breaker. NPI include mandatory mask wearing, hand hygiene, social distancing, and closure of schools and workplaces. Considering the similar mode of transmission of COVID-19 and other pathogens related to acute respiratory infections (ARI), the effects of NPI could possibly lead to decreased ARI attendances in the community. This study aims to determine the year-on-year and weekly changes of ARI attendances across a cluster of polyclinics following the implementation of NPI.

Methods

The effect of the nation-wide measures on the health-seeking behaviour of the study population was examined over three periods: (1) 9 weeks prior to the start of Circuit Breaker (DORSCON Orange period), (2) 8 weeks during the Circuit Breaker, and (3) 9 weeks after easing of Circuit Breaker. Data on ARI attendances for the corresponding periods in 2019 were also extracted for comparison and to assess the seasonal variations of ARI. The average weekly workday ARI attendances were compared with those of the preceding week using Wilcoxon signed rank test.

Results

ARI attendances dropped steadily throughout the study period and were 50–80% lower than in 2019 since Circuit Breaker. They remained low even after Circuit Breaker ended. Positivity rate for influenza-like illnesses samples in the community was 0.0% from the last week of Circuit Breaker to end of study period.

Conclusions

NPI and public education measures during DORSCON Orange and Circuit Breaker periods appear to be associated with the health-seeking behaviour of the public. Changing levels of perceived susceptibility, severity, benefits and barriers, and widespread visual cues based on the Health Belief Model may account for this change. Understanding the impact of NPI and shifts in the public’s health-seeking behaviour will be relevant and helpful in the planning of future pandemic responses.
Association between socio-environmental factors, coverage by family health teams, and rainfall in the spatial distribution of Zika virus infection in the city of Rio de Janeiro, Brazil, in 2015 and 2016
Authors: Raymundo Carlos Eduardo , de Andrade Medronho Roberto
Published: June 2021

Background

Zika virus (ZIKV) infection caused outbreak in Brazil, in 2015 and 2016. Disorganized urban growth, facilitates the concentration of numerous susceptible and infected individuals. It is useful to understand the mechanisms that can favor the increase in ZIKV incidence, such as areas with wide socioeconomic and environmental diversity. Therefore, the study analyzed the spatial distribution of ZIKV in the city of Rio de Janeiro, Brazil, in 2015 and 2016, and associations between the incidence per 1000 inhabitants and socio-environmental factors.

Methods

The census tracts were used as the analytical units reported ZIKV cases among the city’s inhabitants. Local Empirical Bayesian method was used to control the incidence rates’ instability effect. The spatial autocorrelation was verified with Moran’s Index and local indicators of spatial association (LISA). Spearman correlation matrix was used to indicate possible collinearity. The Ordinary Least Squares (OLS), Spatial Lag Model (SAR), and Spatial Error Model (CAR) were used to analyze the relationship between ZIKV and socio-environmental factors.

Results

The SAR model exhibited the best parameters: R2 = 0.44, Log-likelihood = − 7482, Akaike Information Criterion (AIC) = 14,980. In this model, mean income between 1 and 2 minimum wages was possible risk factors for Zika occurrence in the localities. Household conditions related to adequate water supply and the existence of public sewage disposal were associated with lower ZIKV cumulative incidence, suggesting possible protective factors against the occurrence of ZIKV in the localities. The presence of the Family Health Strategy in the census tracts was positively associated with the ZIKV cumulative incidence. However, the results show that mean income less than 1 minimum wage were negatively associated with higher ZIKV cumulative incidence.

Conclusion

The results demonstrate the importance of socio-environmental variables in the dynamics of ZIKV transmission and the relevance for the development of control strategies.
Safety and efficacy of single CHAP Hyaluronan injection versus three injections of linear Hyaluronan in pain relief for knee osteoarthritis: a prospective, 52-week follow-up, randomized, evaluator-blinded study
Authors: Huang Teng-Le , Tsai Chun-Hao
Published: June 2021

Background

The hyaluronic acid (HA) injections are widely used in knee osteoarthritis (OA) patients. We conducted the study comparing the efficacy and safety of single injection of Crosslinked Hyaluronic Acid Platform Hyaluronan (CHAP-HA) with 3-injection of linear hyaluronan in knee OA patients.

Methods

This was a randomized two-arms, evaluator-blinded, controlled, single-center study. Participants with knee OA received single CHAP-HA or three-injection of linear-HA. The 140 patients aged 35–85 years with radiographically confirmed knee OA were enrolled. At week 4, 12, 26, 39, and 52, visual analog scale (VAS) pain score, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index, timed up and go (TUG) and subject’s adverse events (AE) of these 2 groups were recorded. Primary outcome of the differences of VAS pain score at week 26 between groups was analyzed with analysis of covariance (ANCOVA). At week 52, those who met the inclusion criteria could receive a CHAP-HA injection and being followed-up for the adverse events for 4 weeks.

Results

The trial was conducted from September 2015 to April 2017. A total 140 subjects were available for analysis (71 in the CHAP-HA group and 69 in the linear-HA group). At 26th week, there were significant more improvements in VAS pain scores in CHAP-HA compared with linear-HA. Both CHAP-HA and linear-HA showed significant improvements in the VAS pain score at week 26 compared with the baseline, and the occurrence of adverse events during the study period showed no between-group difference. In subjects with KL = 2, both groups showed significant improvements in VAS pain scores within 26 weeks. In patients with KL = 3, only CHAP-HA group showed significant improvement in VAS pain from 4 to 39 weeks. No unexpected or severe AEs were reported.

Conclusions

A single injection of CHAP-HA may be safe and more effective for 26 weeks in patients with knee OA by comparing to linear-HA; moreover, the pain relief effect of CHAP-HA may remain until 52 weeks. For patients with more severe OA, CHAP-HA was demonstrated to be more preferable to relieve OA pain. Furthermore, repeat treatment of CHAP-HA or using CHAP-HA after a three-injection HA was proved to be safe.

Trial registration

ClinicalTrials.gov: NCT03643588. Date: August 23, 2018 (retrospectively registered).

Level of Evidence: Therapeutic Level I.
Type 2 diabetes and its characteristics are associated with poor oral health: findings from 60,590 senior women from the E3N study
Authors: Laouali Nasser , El Fatouhi Douae , Aguayo Gloria , Balkau Beverley , Boutron-Ruault Marie-Christine , Bonnet Fabrice , Fagherazzi Guy
Published: June 2021

Background

Type 2 diabetes (T2D) has been identified as a risk factor for poor oral health, however, a limited number of oral health and T2D characteristics have been studied so far. We sought to assess T2D status, age at diagnosis, duration since diagnosis and treatment in relation to a variety of oral diseases.

Methods

Cross-sectional data were analyzed from the E3N (Etude Epidémiologique auprès de femmes de l'Education Nationale) cohort study which enrolled 60,590 women. Participants self-reported oral health status, and T2D cases were identified using diabetes-specific questionnaires and drug reimbursement insurance databases. Multivariable-adjusted ORs and 95% CIs were estimated using logistic regression models.

Results

The mean age (SD) of the women was 70 years (7.2), and 4.7% (n = 2857) had T2D. Compared to women without T2D, women with T2D were more likely to report a poor perceived oral health (OR 1.37 [95% CI 1.18, 1.60]), wearing dental prostheses (1.26 [1.14, 1.39]) and having problems of biting and chewing food (1.19 [1.07, 1.33]). In addition, for women with T2D the age at diagnosis (inversely) and the duration (positively) were associated with the likelihood to report poor oral health.

Conclusions

For women with T2D, duration and age at diagnosis are associated with wearing prostheses, problems of biting and chewing, periodontitis and gingivitis.
The Plasmodium falciparum Rh5 invasion protein complex reveals an excess of rare variant mutations
Authors: Ndwiga Leonard , Osoti Victor , Ochwedo Kevin Omondi , Wamae Kevin , Bejon Philip , Rayner Julian C. , Githinji George , Ochola-Oyier Lynette Isabella
Published: June 2021

Background

The invasion of the red blood cells by Plasmodium falciparum merozoites involves the interplay of several proteins that are also targets for vaccine development. The proteins PfRh5-PfRipr-PfCyRPA-Pfp113 assemble into a complex at the apical end of the merozoite and are together essential for erythrocyte invasion. They have also been shown to induce neutralizing antibodies and appear to be less polymorphic than other invasion-associated proteins, making them high priority blood-stage vaccine candidates. Using available whole genome sequencing data (WGS) and new capillary sequencing data (CS), this study describes the genetic polymorphism in the Rh5 complex in P. falciparum isolates obtained from Kilifi, Kenya.

Methods

162 samples collected in 2013 and 2014 were genotyped by capillary sequencing (CS) and re-analysed WGS from 68 culture-adapted P. falciparum samples obtained from a drug trial conducted from 2005 to 2007. The frequency of polymorphisms in the merozoite invasion proteins, PfRh5, PfRipr, PfCyRPA and PfP113 were examined and where possible polymorphisms co-occurring in the same isolates.

Results

From a total 70 variants, including 2 indels, 19 SNPs [27.1%] were identified by both CS and WGS, while an additional 15 [21.4%] and 36 [51.4%] SNPs were identified only by either CS or WGS, respectively. All the SNPs identified by CS were non-synonymous, whereas WGS identified 8 synonymous and 47 non-synonymous SNPs. CS identified indels in repeat regions in the p113 gene in codons 275 and 859 that were not identified in the WGS data. The minor allele frequencies of the SNPs ranged between 0.7 and 34.9% for WGS and 1.1–29.6% for CS. Collectively, 12 high frequency SNPs (> 5%) were identified: four in Rh5 codon 147, 148, 203 and 429, two in p113 at codons 7 and 267 and six in Ripr codons 190, 259, 524, 985, 1003 and 1039.

Conclusion

This study reveals that the majority of the polymorphisms are rare variants and confirms a low level of genetic polymorphisms in all proteins within the Rh5 complex.
Novel CD44-targeting and pH/redox-dual-stimuli-responsive core–shell nanoparticles loading triptolide combats breast cancer growth and lung metastasis
Authors: Shi Jinfeng , Ren Yali , Ma Jiaqi , Luo Xi , Li Jiaxin , Wu Yihan , Gu Huan , Fu Chaomei , Cao Zhixing , Zhang Jinming
Published: June 2021

Background

The toxicity and inefficient delivery of triptolide (TPL) in tumor therapy have greatly limited the clinical application. Thus, we fabricated a CD44-targeting and tumor microenvironment pH/redox-sensitive nanosystem composed of hyaluronic acid-vitamin E succinate and poly (β-amino esters) (PBAEss) polymers to enhance the TPL-mediated suppression of breast cancer proliferation and lung metastasis.

Results

The generated TPL nanoparticles (NPs) had high drug loading efficiency (94.93% ± 2.1%) and a desirable average size (191 nm). Mediated by the PBAEss core, TPL/NPs displayed a pH/redox-dual-stimuli-responsive drug release profile in vitro. Based on the hyaluronic acid coating, TPL/NPs exhibited selective tumor cellular uptake and high tumor tissue accumulation capacity by targeting CD44. Consequently, TPL/NPs induced higher suppression of cell proliferation, blockage of proapoptotic and cell cycle activities, and strong inhibition of cell migration and invasion than that induced by free TPL in MCF-7 and MDA-MB-231 cells. Importantly, TPL/NPs also showed higher efficacy in shrinking tumor size and blocking lung metastasis with decreased systemic toxicity in a 4T1 breast cancer mouse model at an equivalent or lower TPL dosage compared with that of free TPL. Histological immunofluorescence and immunohistochemical analyses in tumor and lung tissue revealed that TPL/NPs induced a high level of apoptosis and suppressed expression of matrix metalloproteinases, which contributed to inhibiting tumor growth and pulmonary metastasis.

Conclusion

Collectively, our results demonstrate that TPL/NPs, which combine tumor active targeting and pH/redox-responsive drug release with proapoptotic and antimobility effects, represent a promising candidate in halting breast cancer progression and metastasis while minimizing systemic toxicity.

Graphic Abstract
Fe-doped chrysotile nanotubes containing siRNAs to silence SPAG5 to treat bladder cancer
Authors: Liu Jianye , Zhang Yi , Zeng Hongliang , Wang Long , Zhang Qun , Wu Pei , Liu Xiaoming , Xie Hongyi , Xiang Wei , Liu Biao , Liu Jiahao , Liu Xuewen , Xie Jianfei , Tang Jin , Long Zhi , He Leye , Xiao Mengqing , Xiang Liang , Cao Ke
Published: June 2021

Background

For certain human cancers, sperm associated antigen 5 (SPAG5) exerts important functions for their development and progression. However, whether RNA interference (RNAi) targeting SPAG5 has antitumor effects has not been determined clinically.

Results

The results indicated that Fe-doped chrysotile nanotubes (FeSiNTs) with a relatively uniform outer diameter (15–25 nm) and inner diameter (7–8 nm), and a length of several hundred nanometers, which delivered an siRNA against the SPAG5 oncogene (siSPAG5) efficiently. The nanomaterials were designed to prolong the half-life of siSPAG5 in blood, increase tumor cell-specific uptake, and maximize the efficiency of SPAG5 silencing. In vitro, FeSiNTs carrying siSPAG5 inhibited the growth, migration, and invasion of bladder cancer cells. In vivo, the FeSiNTs inhibited growth and metastasis in three models of bladder tumors (a tail vein injection lung metastatic model, an in-situ bladder cancer model, and a subcutaneous model) with no obvious toxicities. Mechanistically, we showed that FeSiNTs/siSPAG5 repressed PI3K/AKT/mTOR signaling, which suppressed the growth and progression of tumor cells.

Conclusions

The results highlight that FeSiNTs/siSPAG5 caused no activation of the innate immune response nor any systemic toxicity, indicating the possible therapeutic utility of FeSiNTs/siSPAG5 to deliver siSPAG5 to treat bladder cancer.

Graphic abstract
“If I knew I could get that every hour instead of alcohol, I would take the cannabis”: need and feasibility of cannabis substitution implementation in Canadian managed alcohol programs
Authors: Pauly Bernie , Brown Meaghan , Chow Clifton , Wettlaufer Ashley ,   East Side Illicit Drinkers Group for Education (EIDGE), Graham Brittany , Urbanoski Karen , Callaghan Russell , Rose Cindy , Jordan Michelle , Stockwell Tim , Thomas Gerald , Sutherland Christy
Published: June 2021

Background

While there is robust evidence for strategies to reduce harms of illicit drug use, less attention has been paid to alcohol harm reduction for people experiencing severe alcohol use disorder (AUD), homelessness, and street-based illicit drinking. Managed Alcohol Programs (MAPs) provide safer and regulated sources of alcohol and other supports within a harm reduction framework. To reduce the impacts of heavy long-term alcohol use among MAP participants, cannabis substitution has been identified as a potential therapeutic tool.

Methods

To determine the feasibility of cannabis substitution, we conducted a pre-implementation mixed-methods study utilizing structured surveys and open-ended interviews. Data were collected from MAP organizational leaders (n = 7), program participants (n = 19), staff and managers (n = 17) across 6 MAPs in Canada. We used the Consolidated Framework for Implementation Research (CFIR) to inform and organize our analysis.

Results

Five themes describing feasibility of CSP implementation in MAPs were identified. The first theme describes the characteristics of potential CSP participants. Among MAP participants, 63% (n = 12) were already substituting cannabis for alcohol, most often on a weekly basis (n = 8, 42.1%), for alcohol cravings (n = 15, 78.9%,) and withdrawal (n = 10, 52.6%). Most MAP participants expressed willingness to participate in a CSP (n = 16, 84.2%). The second theme describes the characteristics of a feasible and preferred CSP model according to participants and staff. Participants preferred staff administration of dry, smoked cannabis, followed by edibles and capsules with replacement of some doses of alcohol through a partial substitution model. Themes three and four highlight organizational and contextual factors related to feasibility of implementing CSPs. MAP participants requested peer, social, and counselling supports. Staff requested education resources and enhanced clinical staffing. Critically, program staff and leaders identified that sustainable funding and inexpensive, legal, and reliable sourcing of cannabis are needed to support CSP implementation.

Conclusion

Cannabis substitution was considered feasible by all three groups and in some MAPs residents are already using cannabis. Partial substitution of cannabis for doses of alcohol was preferred. All three groups identified a need for additional supports for implementation including peer support, staff education, and counselling. Sourcing and funding cannabis were identified as primary challenges to successful CSP implementation in MAPs.