bluuebunny/crossref_metadata_2025 huggingface dataset:
Doctor-patient communication skills: a survey on knowledge and practice of Iranian family physicians
Authors: Shiraly Ramin , Mahdaviazad Hamideh , Pakdin Ali
Published: June 2021

Background

Communication skills are fundamental to successful medical practice and can greatly impact patient satisfaction, compliance and outcomes. This study evaluated knowledge and practice of doctor- patient communication among the urban family physicians based on main items of Calgary Cambridge Observation Guides.

Method

This cross-sectional study was conducted from July to September, 2019, in a 400 randomly selected sample of family physicians of Shiraz, Fars province. The data collection tool was a self-administered, second-part questionnaire developed by the researchers. Participants were asked about their age, gender, practice setting, and years of work experience and if they received any formal training in doctor- patient communication. Data were analyzed using SPSS (Version 16, SPSS Inc., Chicago, IL, USA). A p-value of less than 0.05 was considered statistically significant.

Results

The study participants included 204 male and 196 female family physicians with a mean age of 46.7 ± 7.7 years. The mean communication skills knowledge score was 41.5 (SD: ± 2.8) indicating a high level of knowledge. The mean score for practices was 38.7 (SD: ± 3.4), implying a moderate level of practice. Based on Bloom’s scale, nearly 80% of family physicians had good knowledge about doctor-patient communication skills, however, 55% of participants reported moderate to poor level of practice in this regard. Results of multivariate regression analysis suggest that higher levels of related knowledge, having higher age or longer work experience, and working in the public sector can predict better practice scores (P < 0.005).

Conclusion

There is a potential gap between knowledge and self-reported practices toward communication skills among a sample of Iranian family physicians. They have fundamental weakness in the most important evidence-based items of doctor- patient communication. Considering significant role of family physicians in prevention and control of non-communicable diseases (NCDs) as an emerging challenge of our country, the topic of communication skills should be inserted as a top educational priority of family physicians.
Phenotypic and molecular characterization of pyrazinamide resistance among multidrug-resistant Mycobacterium tuberculosis isolates in Ningbo, China
Authors: Che Yang , Bo Dingyi , Lin Xiang , Chen Tong , He Tianfeng , Lin Yi
Published: June 2021

Background

Detection of pyrazinamide (PZA) resistance in Mycobacterium tuberculosis (TB) patients is critical, especially in dealing with multidrug-resistant Mycobacterium tuberculosis (MDR-TB) case. Up to date, PZA drug susceptibility testing (DST) has not been regularly performed in China. The prevalence and molecular characteristics of PZA resistance in M.tuberculosis isolates, especially MDR-TB have not been studied in Ningbo, China. This study aimed to analyze the phenotypic and molecular characterization of PZA resistance among MDR-TB isolates in Ningbo.

Methods

A total of 110 MDR-TB isolates were collected from the TB patients who were recorded at local TB dispensaries in Ningbo. All clinical isolates were examined by drug susceptibility testing and genotyping. DNA sequencing was used to detect mutations in the pncA gene associated with PZA resistance.

Results

The prevalence of PZA resistance among MDR-TB strains in Ningbo was 59.1%. With regard to the history and the outcome of treatments among MDR-TB cases, the percentages of re-treated MDR-TB patients in the PZA-resistant group and of successful patients in PZA-susceptible group were significantly higher than the ones in the PZA-susceptible group and in the PZA-resistant group, respectively (P = 0.027, P = 0.020). The results showed that the resistance of streptomycin (67.7% vs 46.7%, P = 0.027), ethambutol (56.9% vs 33.3%, P = 0.015), ofloxacin (43.1% vs 11.1%, P = 0.000), levofloxacin (43.1% vs 11.1%, P = 0.000), pre-XDR (pre-Xtensively Drug Resistance) (38.5% vs 15.6%, P = 0.009), were more frequently adverted among PZA-resistant isolates compared with PZA-susceptible isolates. In addition, 110 MDR-TB was composed of 87 (PZA resistant, 78.5%) Beijing strains and 23 (PZA resistant, 21.5%) non-Beijing strains. Fifty-four out of 65 (83.1%) PZA-resistant MDR strains harbored a mutation located in the pncA gene and the majority (90.7%) were point mutations. Compared with the phenotypic characterization, DNA sequencing of pncA has sensitivity and specificity of 83.1 and 95.6%.

Conclusion

The mutations within pncA gene was the primary mechanism of PZA resistance among MDR-TB and DNA sequencing of pncA gene could provide a rapid detection evidence in PZA drug resistance of MDR-TB in Ningbo.
Whether sutures reduce the graft laceration caused by interference screw in anterior cruciate ligament reconstruction? A biomechanical study in vitro
Authors: Teng Yuanjun , Zhang Xiaohui , Da Lijun , Hu Jie , Wang Hong , Han Hua , Wu Meng , Zhang Shifeng , Xia Yayi
Published: June 2021

Background

Interference screw is commonly used for graft fixation in anterior cruciate ligament (ACL) reconstruction. However, previous studies had reported that the insertion of interference screws significantly caused graft laceration. The purposes of this study were to (1) quantitatively evaluate the graft laceration from one single insertion of PEEK interference screws; and (2) determine whether different types of sutures reduced the graft laceration after one single insertion of interference screws in ACL reconstruction.

Methods

The in-vitro ACL reconstruction model was created using porcine tibias and bovine extensor digitorum tendons of bovine hind limbs. The ends of grafts were sutured using three different sutures, including the bioabsorbable, Ethibond and ultra-high molecular weight polyethylene (UHMWPE) sutures. Poly-ether-ether-ketone (PEEK) interference screws were used for tibial fixation. This study was divided into five groups (n = 10 in each group): the non-fixed group, the non-sutured group, the absorbable suture group, the Ethibond suture group and the UHMWPE suture group. Biomechanical tests were performed using the mode of pull-to-failure loading tests at 10 mm/min. Tensile stiffness (newtons per millimeter), energy absorbed to failure (in joules) and ultimate load (newtons) were recorded for analysis.

Results

All prepared tendons and bone specimens showed similar characteristics (length, weight, and pre-tension of the tendons, tibial bone mineral density) among all groups (P > 0.05). The biomechanical tests demonstrated that PEEK interference screws significantly caused the graft laceration (P < 0.05). However, all sutures (the bioabsorbable, Ethibond and UHMWPE sutures) did not reduce the graft laceration in ACL reconstruction (P > 0.05).

Conclusions

Our biomechanical study suggested that the ultimate failure load of grafts was reduced of approximately 25 % after one single insertion of a PEEK interference screw in ACL reconstruction. Suturing the ends of the grafts using different sutures (absorbable, Ethibond and UHMWPE sutures) did not decrease the graft laceration caused by interference screws.
Complications associated with hyperextension bicondylar tibial plateau fractures: a retrospective study
Authors: Bu Guoyun , Sun Weitang , Lu Yandong , Cui Meng , Zhang Xi , Lu Jie , Zhang Jinli , Sun Jie
Published: June 2021

Background

Hyperextension bicondylar tibial plateau fracture (HBTPF) is a particular form of tibial plateau fracture which has gained increasing interest recently but were rarely documented. In this study, we reported the characteristics, clinical intervention, and therapeutic outcomes of HBTPF patients.

Methods

From May 2015 to October 2017, clinical data of consecutive patients with bicondylar tibial plateau fractures (BTPF) who underwent surgical treatment in our hospital were retrospectively studied. The patients were allocated to either the HBTPF group (study group) or the non-HBTPF group (control group) based on the radiological features, and inclusion and exclusion criteria. Demographics, characteristics of knee joint injuries, complications, and outcomes were compared between the two groups.

Results

In total, 59 patients were included in this study. Among them, 17 patients with HBTPF were identified and 42 patients were diagnosed as non-HBTPF. No differences in age, sex, cause of injury, side of injury, site of injury, nerve injury, operation time, and treatment time and incision complication between HBTPF and non-HBTPF group. The incidence rate of popliteal artery injury in HBTPF group was 29.4 %, which was significantly higher than that of non-HBTPF group. Small bone chips on the lateral film were found in 94.1 % of the patients in HBTPF group, which was significantly higher than that of non-HBTPF group. The range of motion (ROM) and hospital for special surgery (HSS) score of HBTPF group were significantly lower than those of non-HBTPF group.

Conclusions

HBTPF is a severe injury with a higher incidence rate of popliteal artery injury and worse outcomes than non-HBTPF. Small bone chips at the anterior margin of the proximal tibia on the lateral plain film might be a characteristic of HBTPF.
Uptake of new antidiabetic medicines in 11 European countries
Authors: Mardetko Nika , Nabergoj Makovec Urska , Locatelli Igor , Janez Andrej , Kos Mitja
Published: June 2021

Background

Several new antidiabetic medicines (GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors) have been approved by the European Medicines Agency since 2006. The aim of this study was to evaluate the uptake of new antidiabetic medicines in European countries over a 10-year period.

Methods

The study used IQVIA quarterly value and volume sales data January 2006–December 2016. The market uptake of new antidiabetic medicines together with intensity of prescribing policy for all antidiabetic medicines were estimated for Austria, Croatia, France, Germany, Hungary, Italy, Poland, Slovenia, Spain, Sweden, and the United Kingdom. The following measures were determined: number of available new active substances, median time to first continuous use, volume market share, and annual therapy cost.

Results

All countries had at least one new antidiabetic medicine in continuous use and an increase in intensity of prescribing policy for all antidiabetic medicines was observed. A tenfold difference in median time to first continuous use (3–30 months) was found. The annual therapy cost in 2016 of new antidiabetic medicines ranged from EUR 363 to EUR 769. Among new antidiabetic medicines, the market share of DPP-4 inhibitors was the highest. Countries with a higher volume market share of incretin-based medicines (Spain, France, Austria, and Germany) in 2011 had a lower increase in intensity of prescribing policy. This kind of correlation was not found in the case of SGLT-2 inhibitors.

Conclusions

This study found important differences and variability in the uptake of new antidiabetic medicines in the included countries.
The impact of caries status on supragingival plaque and salivary microbiome in children with mixed dentition: a cross-sectional survey
Authors: Yang Xiaoxia , He Lidan , Yan Siqi , Chen Xinyi , Que Guoying
Published: June 2021

Background

Supragingival plaque and saliva are commonly used for microbiome analysis. Many epidemiological studies have identified deciduous teeth caries as a risk factor for caries development in first permanent molar (FPM); nevertheless, to the best of our knowledge, there are no reports on the effects of deciduous teeth caries on the microbiome of healthy FPM. Additionally, it remains unclear whether saliva can be used instead of supragingival plaque for caries microbial studies. Therefore, we aimed to elucidate this issue, and to characterize and compare the oral microbiome of healthy FPMs in children with different caries statuses and that from children with and without caries in a similar microhabitat, by PacBio sequencing. Currently, few studies have investigated the oral microbiome of children using this technique.

Methods

Thirty children (aged 7–9 years) with mixed dentition were enrolled; 15 had dental caries, and 15 did not. Supragingival plaques of deciduous molars and maxillary FPMs, and non-stimulating saliva samples were collected. DNA was extracted and the v1–v9 regions of 16S rRNA were amplified. Subsequently, PacBio sequencing and bioinformatic analyses were performed for microbiome identification.

Results

The microbial alpha diversity of the saliva samples was lower than that of the supragingival plaque (p < 0.05); however, no differences were detected between deciduous teeth and FPMs (p > 0.05). In addition, the alpha and beta diversity of children with and without caries was also similar (p > 0.05). Nonmetric multidimensional scaling and Adonis analyses indicated that the microbial structure of salivary and supragingival plaque samples differ (p < 0.05). Further analysis of deciduous teeth plaque showed that Streptococcus mutans, Propionibacterium acidifaciens, and Veillonella dispar were more abundant in children with caries than in those without (p < 0.05); while in FPMs plaque, Selenomonas noxia was more abundant in healthy children (p < 0.05). No differences in microorganisms abundance were found in the saliva subgroups (p > 0.05).

Conclusion

We have determined that supragingival plaque was the best candidate for studying carious microbiome. Furthermore, S. mutans, V. dispar, and P. acidifaciens were highly associated with deciduous teeth caries. S. noxia may be associated with the abiding health of FPM; however, this requires additional studies.
Documentation of older people’s end-of-life care in the context of specialised palliative care: a retrospective review of patient records
Authors: Sjöberg M. , Edberg A.-K. , Rasmussen B. H. , Beck I.
Published: June 2021

Background

Palliative care focuses on identifying, from a holistic perspective, the needs of those experiencing problems associated with life-threatening illnesses. As older people approach the end of their lives, they can experience a complex series of problems that health-care professionals must identify and document in their patients’ records. Documentation is thus important for ensuring high-quality patient care. Previous studies of documentation in older people’s patient records performed in various care contexts have shown that such documentation almost exclusively concerns physical problems. This study explores, in the context of Swedish specialised palliative care, the content of documentation in older people’s patient records, focusing on documented problems, wishes, aspects of wellbeing, use of assessment tools, interventions, and documentation associated with the person’s death.

Methods

A retrospective review based on randomly selected records (n = 92) of older people receiving specialised palliative care, at home or in a palliative in-patient ward, who died in 2017. A review template was developed based on the literature and on a review of sampled records of patients who died the preceding year. The template was checked for inter-rater agreement and used to code all clinical notes in the patients’ records. Data were processed using descriptive statistics.

Results

The most common clinical notes in older people’s patient records concerned interventions (n = 16,031, 71%), mostly related to pharmacological interventions (n = 4318, 27%). The second most common clinical notes concerned problems (n = 2804, 12%), pain being the most frequent, followed by circulatory, nutrition, and anxiety problems. Clinical notes concerning people’s wishes and wellbeing-related details were documented, but not frequently. Symptom assessment tools, except for pain assessments, were rarely used. More people who received care in palliative in-patient wards died alone than did people who received care in their own homes.

Conclusions

Identifying and documenting the complexity of problems in a more structured and planned way could be a method for implementing a more holistic approach to end-of-life care. Using patient-reported outcome measures capturing more than one symptom or problem, and a systematic documentation structure would help in identifying unmet needs and developing holistic documentation of end-of-life care.
Brief Engagement and Acceptance Coaching for Hospice Settings (the BEACHeS study): results from a Phase I study of acceptability and initial effectiveness in people with non-curative cancer
Authors: Hulbert-Williams Nicholas J. , Norwood Sabrina F. , Gillanders David , Finucane Anne M. , Spiller Juliet , Strachan Jenny , Millington Susan , Kreft Joseph , Swash Brooke
Published: June 2021

Objectives

Transitioning into palliative care is psychologically demanding for people with advanced cancer, and there is a need for acceptable and effective interventions to support this. We aimed to develop and pilot test a brief Acceptance and Commitment Therapy (ACT) based intervention to improve quality of life and distress.

Methods

Our mixed-method design included: (i) quantitative effectiveness testing using Single Case Experimental Design (SCED), (ii) qualitative interviews with participants, and (iii) focus groups with hospice staff. The five-session, in-person intervention was delivered to 10 participants; five completed at least 80%.

Results

At baseline, participants reported poor quality of life but low distress. Most experienced substantial physical health deterioration during the study. SCED analysis methods did not show conclusively significant effects, but there was some indication that outcome improvement followed changes in expected intervention processes variables. Quantitative and qualitative data together demonstrates acceptability, perceived effectiveness and safety of the intervention. Qualitative interviews and focus groups were also used to gain feedback on intervention content and to make design recommendations to maximise success of later feasibility trials.

Conclusions

This study adds to the growing evidence base for ACT in people with advanced cancer. A number of potential intervention mechanisms, for example a distress-buffering hypothesis, are raised by our data and these should be addressed in future research using randomised controlled trial designs. Our methodological recommendations—including recruiting non-cancer diagnoses, and earlier in the treatment trajectory—likely apply more broadly to the delivery of psychological intervention in the palliative care setting.

This study was pre-registered on the Open Science Framework (Ref: 46,033) and retrospectively registered on the ISRCTN registry (Ref: ISRCTN12084782).
The knowledge about patient safety among undergraduate nurse students in Cyprus and Greece: a comparative study
Authors: Dimitriadou Maria , Merkouris Anastasios , Charalambous Andreas , Lemonidou Chrysoula , Papastavrou Evridiki
Published: June 2021

Background

The Patient safety movement contributed to the reduction of preventable adverse events associated with health care. Although patient safety issues have received the attention of educators in the health care studies, there is evidence that in nursing education and the associated curricula it is not well-incorporated. This may not allow students to acquire scientific knowledge and develop strong competencies to assure patient safety throughout their professional life. The aım of the study was the exploration of the undergraduate nursing student perspectives regarding knowledge received during their training about patient safety-related issues.

Methods

A descriptive comparative study was conducted with three and four-year undergraduate nursing students from the Cyprus Republic (n = 243) and Greece (n = 367). All students were surveyed using the Health Professional Education Patient Safety Survey (H-PEPSS) to describe students’ knowledge in the classroom and clinical setting.

Results

Students’ Knowledge about patient safety was expressed significantly higher (p < 0.001) in the classroom (mean = 4.0) than the clinical setting (3.7) (1–5 scale). The knowledge in the dimension “clinical aspects” received the highest score and “working in teams” received the lowest. Also, differences were recorded between countries wıth Cypriot students reporting hıgher level of knowledge than the Greek students in most of the dimensions.

Conclusıon

The findings revealed the gap between theory and practice and the need for collaboration between the two settings. Also, students reported relatively higher knowledge with regards to the technical aspects of patient safety. Still, they were less knowledgable about the sociocultural aspects of the patient, such as working in teams.
Dynamics of Verticillium dahliae race 1 population under managed agricultural ecosystems
Authors: Chen Jie-Yin , Zhang Dan-Dan , Huang Jin-Qun , Li Ran , Wang Dan , Song Jian , Puri Krishna D. , Yang Lin , Kong Zhi-Qiang , Tong Bang-Zhuo , Li Jun-Jiao , Huang Yu-Shan , Simko Ivan , Klosterman Steven J. , Dai Xiao-Feng , Subbarao Krishna V.
Published: June 2021

Background

Plant pathogens and their hosts undergo adaptive changes in managed agricultural ecosystems, by overcoming host resistance, but the underlying genetic adaptations are difficult to determine in natural settings. Verticillium dahliae is a fungal pathogen that causes Verticillium wilt on many economically important crops including lettuce. We assessed the dynamics of changes in the V. dahliae genome under selection in a long-term field experiment.

Results

In this study, a field was fumigated before the Verticillium dahliae race 1 strain (VdLs.16) was introduced. A derivative 145-strain population was collected over a 6-year period from this field in which a seggregating population of lettuce derived from Vr1/vr1 parents were evaluated. We de novo sequenced the parental genome of VdLs.16 strain and resequenced the derivative strains to analyze the genetic variations that accumulate over time in the field cropped with lettuce. Population genomics analyses identified 2769 single-nucleotide polymorphisms (SNPs) and 750 insertion/deletions (In-Dels) in the 145 isolates compared with the parental genome. Sequence divergence was identified in the coding sequence regions of 378 genes and in the putative promoter regions of 604 genes. Five-hundred and nine SNPs/In-Dels were identified as fixed. The SNPs and In-Dels were significantly enriched in the transposon-rich, gene-sparse regions, and in those genes with functional roles in signaling and transcriptional regulation.

Conclusions

Under the managed ecosystem continuously cropped to lettuce, the local adaptation of V. dahliae evolves at a whole genome scale to accumulate SNPs/In-Dels nonrandomly in hypervariable regions that encode components of signal transduction and transcriptional regulation.
Uptake of exogenous estrogen as a differential diagnosis of ovarian-remnant-syndrome in a bitch: a case report
Authors: Ganz Sebastian , Wehrend Axel
Published: June 2021

Background

Clinical signs of heat in bitches that have been previously spayed are often associated with the presence of ovarian remnant syndrome. The inclusion of exogenous estrogens as a differential diagnosis in this regard is often ignored and may lead to misinterpretation of the case.

Case presentation

Herein, we report a case of exogenous estrogen exposure over several months to a 6.5-year-old spayed crossbred bitch, weighing 8.4 kg. The bitch presented in the clinic because of suspected ovarian remnant syndrome. Castration was performed within the first 6 months after birth. Important endocrine parameters measured at the first appointment were Anti-Müllerian hormone (< 0.01 ng/mL), progesterone (0.36 ng/mL), estradiol-17ß (20.7 pg/mL), and luteinizing hormone (< 0.1 ng/mL). After an extensive conversation with the owner, it was revealed that she was using an estrogen spray because of severe menopausal symptoms. After the owner stopped using this spray, the symptoms of the bitch disappeared.

Conclusion

Therefore, the uptake of estrogens should be a differential diagnosis for symptoms of the ovarian remnant syndrome. A detailed anamnesis is crucial to identify the source of estrogen in the environment of the affected bitch.
A comparison of thrombosis in total knee arthroplasty with and without a tourniquet: a meta-analysis of randomized controlled trials
Authors: Xie Jia , Yu Hao , Wang Fangyuan , Jing Juehua , Li Jun
Published: June 2021

Background

Tourniquets are widely used in total knee arthroplasty (TKA), but the issue of their safety remains controversial. Previous studies have focused on TKA blood loss, duration of surgery, and hemostatic drugs. The purpose of this meta-analysis was to analyze the effect of tourniquet use on postoperative deep venous thrombosis (DVT).

Methods

PubMed, SCOPUS, Web of Science, Embase, and the Cochrane Library were searched for randomized clinical trials published before April 17, 2020, that compared the effect of tourniquet use on postoperative DVT, knee circumference, D-dimers, and pain measured using the visual analog scale (VAS).

Results

Fourteen clinical trials that included 1321 unique participants were included in the meta-analysis. Among the total, 721 and 600 participants were randomized to the tourniquet and non-tourniquet groups, respectively. The incidence of postoperative thrombosis in the tourniquet group was significantly higher than in the non-tourniquet group (RR 2.30, 95% CI 1.51–3.49, P < 0.0001, I2 = 0%). On the 1st, 3rd, and 5th to 21st days, and 3 to 6 weeks after surgery, the knee circumference difference of the tourniquet group was significantly larger than that of the non-tourniquet group (P < 0.05). However, 4 to 6 months after the surgery, no significant difference in knee circumference was found between the two groups (MD 0.14, 95% CI −0.02–0.31, P = 0.09, I2 = 0%). The VAS score of the tourniquet group was higher than the non-tourniquet group on the 3rd and 5th days after surgery (P < 0.05). However, this difference was not significant (MD 0.31, 95% CI −0.05–0.66, P = 0.09, I2 = 89%).

Conclusion

Results of this meta-analysis indicate that tourniquet application could increase the incidence of postoperative DVT and aggravate postoperative pain and swelling in the short term.

Level of evidence

Level III
Spatial architecture of the immune microenvironment orchestrates tumor immunity and therapeutic response
Authors: Fu Tong , Dai Lei-Jie , Wu Song-Yang , Xiao Yi , Ma Ding , Jiang Yi-Zhou , Shao Zhi-Ming
Published: June 2021

Tumors are not only aggregates of malignant cells but also well-organized complex ecosystems. The immunological components within tumors, termed the tumor immune microenvironment (TIME), have long been shown to be strongly related to tumor development, recurrence and metastasis. However, conventional studies that underestimate the potential value of the spatial architecture of the TIME are unable to completely elucidate its complexity. As innovative high-flux and high-dimensional technologies emerge, researchers can more feasibly and accurately detect and depict the spatial architecture of the TIME. These findings have improved our understanding of the complexity and role of the TIME in tumor biology. In this review, we first epitomized some representative emerging technologies in the study of the spatial architecture of the TIME and categorized the description methods used to characterize these structures. Then, we determined the functions of the spatial architecture of the TIME in tumor biology and the effects of the gradient of extracellular nonspecific chemicals (ENSCs) on the TIME. We also discussed the potential clinical value of our understanding of the spatial architectures of the TIME, as well as current limitations and future prospects in this novel field. This review will bring spatial architectures of the TIME, an emerging dimension of tumor ecosystem research, to the attention of more researchers and promote its application in tumor research and clinical practice.
A systematic review on poly(I:C) and poly-ICLC in glioblastoma: adjuvants coordinating the unlocking of immunotherapy
Authors: De Waele Jorrit , Verhezen Tias , van der Heijden Sanne , Berneman Zwi N. , Peeters Marc , Lardon Filip , Wouters An , Smits Evelien L. J. M.
Published: June 2021

Immunotherapy is currently under intensive investigation as a potential breakthrough treatment option for glioblastoma. Given the anatomical and immunological complexities surrounding glioblastoma, lymphocytes that infiltrate the brain to develop durable immunity with memory will be key. Polyinosinic:polycytidylic acid, or poly(I:C), and its derivative poly-ICLC could serve as a priming or boosting therapy to unleash lymphocytes and other factors in the (immuno)therapeutic armory against glioblastoma. Here, we present a systematic review on the effects and efficacy of poly(I:C)/poly-ICLC for glioblastoma treatment, ranging from preclinical work on cellular and murine glioblastoma models to reported and ongoing clinical studies. MEDLINE was searched until 15 May 2021 to identify preclinical (glioblastoma cells, murine models) and clinical studies that investigated poly(I:C) or poly-ICLC in glioblastoma. A systematic review approach was conducted according to PRISMA guidelines.ClinicalTrials.govwas queried for ongoing clinical studies. Direct pro-tumorigenic effects of poly(I:C) on glioblastoma cells have not been described. On the contrary, poly(I:C) changes the immunological profile of glioblastoma cells and can also kill them directly. In murine glioblastoma models, poly(I:C) has shown therapeutic relevance as an adjuvant therapy to several treatment modalities, including vaccination and immune checkpoint blockade. Clinically, mostly as an adjuvant to dendritic cell or peptide vaccines, poly-ICLC has been demonstrated to be safe and capable of eliciting immunological activity to boost therapeutic responses. Poly-ICLC could be a valuable tool to enhance immunotherapeutic approaches for glioblastoma. We conclude by proposing several promising combination strategies that might advance glioblastoma immunotherapy and discuss key pre-clinical aspects to improve clinical translation.
The Retornus-2 study: impact of respiratory muscle training in subacute stroke patients with dysphagia, study protocol of a double-blind randomized controlled trial
Authors: Guillen-Sola A. , Messaggi-Sartor M. , Ramírez-Fuentes C. , Marco E. , Duarte E.
Published: June 2021

Background

Stroke can lead to varying degrees of oropharyngeal dysphagia, respiratory muscle dysfunction and even increase medical complications such as aspiration, malnutrition and death. Recent studies suggest that inspiratory and expiratory respiratory muscle training (IEMT) can improve swallowing efficacy and may reduce aspiration events. The main purpose of this study is to examine whether an 8-week IEMT programme can improve respiratory muscle strength and swallow dysfunction severity in subacute stroke patients with dysphagia.

Methods

Retornus-2 is a two-arm, prospectively registered, randomized controlled study with blinded assessors and the participation of fifty individuals who have suffered a stroke. The intervention group undergoes IEMT training consisting of 5 sets of 10 repetitions, three times a day for 8 weeks. Training loads increase weekly. The control group undergoes a sham-IEMT protocol. The primary outcome examines the efficacy of the IEMT protocol to increase respiratory muscle strength and reduce dysphagia severity. The secondary outcome assesses the longitudinal impact of dysphagia on body composition and nutritional assessment over a 6-month follow-up.

Discussion

IEMT induces an improvement in respiratory muscle strength and might be associated with relevant benefits in dysphagia patterns, as well as a reduction in the number of aspiration events confirmed by videofluoroscopy or fiberoptic endoscopic evaluation of swallowing. The description of the impact of swallowing impairment on nutritional status will help develop new strategies to face this known side-effect.

Trial registration

Clinicaltrials.gov NCT03021252. Registered on 10 January 2017. https://clinicaltrials.gov/ct2/results?cond=retornus+2&term=&cntry=ES&state=&city=&dist=

WHO trial Registration data set: Due to heavy traffic generated by the COVID-19 outbreak, the ICTRP Search Portal does not respond. The portal recommends other registries such as clinicaltrials.gov. Protocol version: RETORNUS 2_ PROTOCOL_2.
Exploiting prunability for person re-identification
Authors: Masson Hugo , Bhuiyan Amran , Nguyen-Meidine Le Thanh , Javan Mehrsan , Siva Parthipan , Ayed Ismail Ben , Granger Eric
Published: June 2021

Recent years have witnessed a substantial increase in the deep learning (DL) architectures proposed for visual recognition tasks like person re-identification, where individuals must be recognized over multiple distributed cameras. Although these architectures have greatly improved the state-of-the-art accuracy, the computational complexity of the convolutional neural networks (CNNs) commonly used for feature extraction remains an issue, hindering their deployment on platforms with limited resources, or in applications with real-time constraints. There is an obvious advantage to accelerating and compressing DL models without significantly decreasing their accuracy. However, the source (pruning) domain differs from operational (target) domains, and the domain shift between image data captured with different non-overlapping camera viewpoints leads to lower recognition accuracy. In this paper, we investigate the prunability of these architectures under different design scenarios. This paper first revisits pruning techniques that are suitable for reducing the computational complexity of deep CNN networks applied to person re-identification. Then, these techniques are analyzed according to their pruning criteria and strategy and according to different scenarios for exploiting pruning methods to fine-tuning networks to target domains. Experimental results obtained using DL models with ResNet feature extractors, and multiple benchmarks re-identification datasets, indicate that pruning can considerably reduce network complexity while maintaining a high level of accuracy. In scenarios where pruning is performed with large pretraining or fine-tuning datasets, the number of FLOPS required by ResNet architectures is reduced by half, while maintaining a comparable rank-1 accuracy (within 1% of the original model). Pruning while training a larger CNNs can also provide a significantly better performance than fine-tuning smaller ones.
Cognitive interventions in children and adolescents from low socioeconomic status backgrounds: a systematic review protocol of randomized controlled trials
Authors: Company-Córdoba Rosalba , Sianes Antonio , Simpson Ian Craig , Ibáñez-Alfonso Joaquín A.
Published: June 2021

Background

Many studies have evaluated the effects that a lack of resources has in children’s physical and cognitive development. Although there are reviews that have focused on applied interventions from different perspectives, there is still a need for a comprehensive review of what has been attempted with these children from the cognitive intervention field. The aim of this paper is to present a protocol for a systematic review collecting randomized controlled trials (RCTs) studies whose purpose was to enhance cognitive development through the implementation of cognitive interventions in children and adolescents (< 18 years old) from low socioeconomic Status (SES) settings.

Methods

The following databases will be searched: Web of Science (WoS core collection), PsycINFO, Cochrane Central Register of Controlled Trial, ERIC, PubMed, ICTRP and Opengrey Register (System for Information of Grey Literature in Europe). Searches will be adapted for each database. Additionally, the reference list of articles included in the review will also be searched. As part of this process, two reviewers will determine, independently, the suitability of each article taking into account predefined inclusion/exclusion criteria. Pertinent data will then be extracted, including sample characteristics, specifics of the intervention, and outcomes, as well as follow-up measures. Internal validity will be assessed using the Cochrane Risk of Bias Tool. A quantitative synthesis of results will be conducted using a meta-analysis. However, if a meta-analysis is difficult to implement due to the diversity of the studies (for example, in terms of measures used to estimate the effect size, intervention types, outcomes, etc.), the technique synthesis without meta-analysis (SWiM) will be used. A description of outcome measures will be provided, as measured by validated neuropsychological instruments of any cognitive function.

Discussion

The systematic review will offer a framework based on evidence to organisations, institutions, and experts who want to implement or promote interventions aimed at enhancing cognitive domains in children and adolescents who live in disadvantaged contexts.

Systematic review registration

This protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 16 March 2020 (registration number: CDR42020150238).
Stable finite difference method for fractional reaction–diffusion equations by compact implicit integration factor methods
Authors: Zhang Rongpei , Li Mingjun , Chen Bo , Zhang Liwei
Published: June 2021

In this paper we propose a stable finite difference method to solve the fractional reaction–diffusion systems in a two-dimensional domain. The space discretization is implemented by the weighted shifted Grünwald difference (WSGD) which results in a stiff system of nonlinear ordinary differential equations (ODEs). This system of ordinary differential equations is solved by an efficient compact implicit integration factor (cIIF) method. The stability of the second order cIIF scheme is proved in the discrete $L^{2}$

L
2

-norm. We also prove the second-order convergence of the proposed scheme. Numerical examples are given to demonstrate the accuracy, efficiency, and robustness of the method.
Effects of floods on macroinvertebrate communities in the Zarin Gol River of northern Iran: implications for water quality monitoring and biological assessment
Authors: Gholizadeh Mohammad
Published: June 2021

Background

The timing, magnitude, and duration of extreme hydrological disasters have the potential to threaten the species diversity and river habitats. On August 8, 2014, and August 19, 2017, disastrous floods struck mountainous regions of Iran’s Zarin Gol River basin. Macroinvertebrate communities were studied at seven upstreams prior to the floods in June 2014 and 2017 and after the floods in September 2014 and 2017 and 9 months after the second flood in June 2018. The effects of floods on macroinvertebrate communities, recovery rate of macroinvertebrate community resilience and influencing factors were investigated.

Results

Despite the fact that extreme floods were the only reason of the disruption, the effects of biological water quality assessment metrics after the disaster were comparable to those of heavily polluted waters. Biological indicators revealed that the communities were unaffected prior to the floods, and the water quality remained within acceptable limits. Following the disasters, the density of macroinvertebrates declined, and biological indicators demonstrated the severe depletion of water quality. Community indicators (species richness, percent model affinity (PMA), and Ephemeroptera, Plecoptera, and Trichoptera (EPT) richness) rebounded after 9 months (June 2018), demonstrating that Zarin Gol River’s macroinvertebrate communities could recover even after the severe impact of the floods. As a result, macroinvertebrate samples taken from flood-affected areas revealed that extreme flooding, rather than a decrease in water quality, causes a loss of diversity and abundance.

Conclusion

Because of shifts in hydrological regimes in streams around the world, understanding the short-term impacts of strong flooding and the comparatively quick recovery of macroinvertebrate ecosystems has important consequences for bio-assessment programs after severe floods.
Development of an unannounced standardized patient protocol to evaluate opioid use disorder treatment in pregnancy for American Indian and rural communities
Authors: Kelley A. Taylor , Smid Marcela C. , Baylis Jacob D. , Charron Elizabeth , Binns-Calvey Amy E. , Archer Shayla , Weiner Saul J. , Begaye Lori Jo , Cochran Gerald
Published: June 2021

Background

Opioid use disorder (OUD) disproportionately impacts rural and American Indian communities and has quadrupled among pregnant individuals nationwide in the past two decades. Yet, limited data are available about access and quality of care available to pregnant individuals in rural areas, particularly among American Indians (AIs). Unannounced standardized patients (USPs), or “secret shoppers” with standardized characteristics, have been used to assess healthcare access and quality when outcomes cannot be measured by conventional methods or when differences may exist between actual versus reported care. While the USP approach has shown benefit in evaluating primary care and select specialties, its use to date for OUD and pregnancy is very limited.

Methods

We used literature review, current practice guidelines for perinatal OUD management, and stakeholder engagement to design a novel USP protocol to assess healthcare access and quality for OUD in pregnancy. We developed two USP profiles—one white and one AI—to reflect our target study area consisting of three rural, predominantly white and AI US counties. We partnered with a local community health center network providing care to a large AI population to define six priority outcomes for evaluation: (1) OUD treatment knowledge among clinical staff answering telephones; (2) primary care clinic facilitation and provision of prenatal care and buprenorphine treatment; (3) appropriate completion of evidence-based screening, symptom assessment, and initial steps in management; (4) appropriate completion of risk factor screening/probing about individual circumstances that may affect care; (5) patient-directed tone, stigma, and professionalism by clinic staff; and (6) disparities in care between whites and American Indians.

Discussion

The development of this USP protocol tailored to a specific environment and high-risk patient population establishes an innovative approach to evaluate healthcare access and quality for pregnant individuals with OUD. It is intended to serve as a roadmap for our own study and for future related work within the context of substance use disorders and pregnancy.
Impaired anaplerosis is a major contributor to glycolysis inhibitor toxicity in glioma
Authors: Khadka Sunada , Arthur Kenisha , Barekatain Yasaman , Behr Eliot , Washington Mykia , Ackroyd Jeffrey , Crowley Kaitlyn , Suriyamongkol Pornpa , Lin Yu-Hsi , Pham Cong-Dat , Zielinski Rafal , Trujillo Marissa , Galligan James , Georgiou Dimitra K. , Asara John , Muller Florian
Published: June 2021

Background

Reprogramming of metabolic pathways is crucial to satisfy the bioenergetic and biosynthetic demands and maintain the redox status of rapidly proliferating cancer cells. In tumors, the tricarboxylic acid (TCA) cycle generates biosynthetic intermediates and must be replenished (anaplerosis), mainly from pyruvate and glutamine. We recently described a novel enolase inhibitor, HEX, and its pro-drug POMHEX. Since glycolysis inhibition would deprive the cell of a key source of pyruvate, we hypothesized that enolase inhibitors might inhibit anaplerosis and synergize with other inhibitors of anaplerosis, such as the glutaminase inhibitor, CB-839.

Methods

We analyzed polar metabolites in sensitive (ENO1-deleted) and resistant (ENO1-WT) glioma cells treated with enolase and glutaminase inhibitors. We investigated whether sensitivity to enolase inhibitors could be attenuated by exogenous anaplerotic metabolites. We also determined the synergy between enolase inhibitors and the glutaminase inhibitor CB-839 in glioma cells in vitro and in vivo in both intracranial and subcutaneous tumor models.

Results

Metabolomic profiling of ENO1-deleted glioma cells treated with the enolase inhibitor revealed a profound decrease in the TCA cycle metabolites with the toxicity reversible upon exogenous supplementation of supraphysiological levels of anaplerotic substrates, including pyruvate. ENO1-deleted cells also exhibited selective sensitivity to the glutaminase inhibitor CB-839, in a manner rescuable by supplementation of anaplerotic substrates or plasma-like media PlasmaxTM. In vitro, the interaction of these two drugs yielded a strong synergistic interaction but the antineoplastic effects of CB-839 as a single agent in ENO1-deleted xenograft tumors in vivo were modest in both intracranial orthotopic tumors, where the limited efficacy could be attributed to the blood-brain barrier (BBB), and subcutaneous xenografts, where BBB penetration is not an issue. This contrasts with the enolase inhibitor HEX, which, despite its negative charge, achieved antineoplastic effects in both intracranial and subcutaneous tumors.

Conclusion

Together, these data suggest that at least for ENO1-deleted gliomas, tumors in vivo—unlike cells in culture—show limited dependence on glutaminolysis and instead primarily depend on glycolysis for anaplerosis. Our findings reinforce the previously reported metabolic idiosyncrasies of in vitro culture and suggest that cell culture media nutrient composition more faithful to the in vivo environment will more accurately predict in vivo efficacy of metabolism targeting drugs.
‘Pediatric Bipolar Disorder’ rates are still lower than claimed: a re-examination of eight epidemiological surveys used by an updated meta-analysis
Authors: Parry Peter , Allison Stephen , Bastiampillai Tarun
Published: June 2021

Background

‘Pediatric bipolar disorder’ (PBD) is a controversial diagnosis with varying rates of clinical diagnosis. A highly cited meta-analysis (Van Meter et al. 2011) of a dozen epidemiological surveys suggested a global community prevalence of PBD of 1.8%. This was updated to 3.9% with eight additional surveys (Van Meter et al. 2019a). In terms of the Cochrane Handbook for Systematic Reviews of Interventions, the heterogenous community surveys were arguably unsuitable for statistical meta-analysis and warranted a narrative analysis. A narrative analysis (Parry et al. 2018) of the original 12 surveys concluded rates of PBD were substantially lower than 1.8% and led to a nine-article debate on the validity, arguable overdiagnosis and iatrogenic aspects of the PBD diagnosis (e.g. Carlson and Dubicka Child Adolesc Mental Health 21:86–87, 2019). This article extends the narrative analysis to include the eight newer community surveys.

Methods

A narrative analysis of the methodologies and the prevalence rates reported by the epidemiological surveys.

Results

Across all twenty surveys there was significant variation in methodologies and reported prevalence rates. Of the eight newer surveys, five (two Brazilian, one English, one Turkish, one United States) provided information of pre-adolescent prevalence rates of bipolar spectrum disorder. These pre-adolescent rates were zero or close to zero. Rates of adolescent hypomania and mania were higher, but follow-up data in two studies suggested hypomania might sometimes achieve prolonged remission or not lead to adult bipolar disorder.

Limitations

Methods in the original surveys vary and criteria used for various bipolar diagnoses were not always fully described. This limitation applies to a narrative analysis but also to a statistical meta-analysis.

Conclusion

Bipolar disorder is very rare in childhood and rare in adolescence. PBD as a diagnostic construct fails to correlate with adult bipolar disorder and the term should be abandoned. Hypomanic syndromes in adolescence may not always progress to adult bipolar disorder. Early diagnosis of bipolar disorder is important, but over-diagnosis risks adverse iatrogenic consequences.