bluuebunny/crossref_metadata_2025 huggingface dataset:
A case of canine renal lymphoma of granular lymphocytes with severe polycythemia
Authors: Kotb Sara , Allende Carolina , O’Neill T. William , Bruckner Krista , DeMorais Helio , Gordon Jana , Curran Kaitlin , Russell Duncan S. , Stieger-Vanegas Susanne M. , Johns Jennifer L.
Published: April 2021

Background

Renal lymphoma in dogs is rare and has a poor prognosis. Granular lymphocyte morphology is rarely reported in canine renal lymphoma. Mild to moderate polycythemia is reported in a number of canine renal lymphoma cases.

Case presentation

A 10-year-old Labrador retriever presented to a university veterinary teaching hospital after a 1-month history of polyuria, polydipsia, and pollakiuria and a 2-week history of abdominal distention, lethargy, and increased respiratory effort. Abdominal ultrasound showed a wedge-shaped to rounded, heterogeneously hypoechoic mass lesion in the left kidney. Cytologic analysis of a percutaneous aspirate of the mass was consistent with lymphoma of granular lymphocytes. Severe polycythemia (hematocrit 0.871) was noted on a complete blood cell count. Clonality analysis identified a clonally rearranged T-cell receptor (TCR) gene and immunohistochemical staining was CD3+, CD79a- and CD11d+, supporting cytotoxic T-cell lymphoma.

Conclusions

To our knowledge, this is the first report of renal cytotoxic T-cell lymphoma with severe polycythemia in a dog. Severe polycythemia and renal cytotoxic T-cell lymphoma are both rare in dogs; this report adds to the body of knowledge on these conditions.
Recombinant pseudorabies virus with gI/gE deletion generated by overlapping polymerase chain reaction and homologous recombination technology induces protection against the PRV variant PRV-GD2013
Authors: Li Wenhui , Zhuang Dijing , Li Hong , Zhao Mengpo , Zhu Erpeng , Xie Baoming , Chen Jinding , Zhao Mingqiu
Published: April 2021

Background

Since 2011, numerous highly virulent and antigenic variant viral strains have been reported in pigs that were vaccinated against the swine pseudorabies virus. These infections have led to substantial economic losses in the Chinese swine industry.

Results

This study, constructed a novel recombinant vaccine strain with gI/gE deletion (PRV-GD2013-ΔgI/gE) by overlapping PCR and homologous recombination technology. The growth curves and plaque morphology of the recombinant virus were similar to those of the parental strain. However, PRV-GD2013-ΔgI/gE infection was significantly attenuated in mice compared with that of PRV-GD2013. Two-week-old piglets had normal rectal temperatures and displayed no clinical symptoms after being inoculated with 105 TCID50 PRV-GD2013-ΔgI/gE, indicating that the recombinant virus was avirulent in piglets. Piglets were immunized with different doses of PRV-GD2013-ΔgI/gE, or a single dose of Bartha-K61 or DMEM, and infected with PRV-GD2013 at 14 days post-vaccination. Piglets given high doses of PRV-GD2013-ΔgI/gE showed no obvious clinical symptoms, and their antibody levels were higher than those of other groups, indicating that the piglets were completely protected from PRV-GD2013.

Conclusions

The PRV-GD2013-ΔgI/gE vaccine strain could be effective for immunizing Chinese swine herds against the pseudorabies virus (PRV) strain.
Expanded noninvasive prenatal testing for fetal aneuploidy and copy number variations and parental willingness for invasive diagnosis in a cohort of 18,516 cases
Authors: Ge Yunsheng , Li Jia , Zhuang Jianlong , Zhang Jian , Huang Yanru , Tan Meihua , Li Wei , Chen Jiayan , Zhou Yulin
Published: April 2021

Background

Noninvasive prenatal testing (NIPT) has been wildly used to screen for common aneuplodies. In recent years, the test has been expanded to detect rare autosomal aneuploidies (RATs) and copy number variations (CNVs). This study was performed to investigate the performance of expanded noninvasive prenatal testing (expanded NIPT) in screening for common trisomies, sex chromosomal aneuploidies (SCAs), rare autosomal aneuploidies (RATs), and copy number variations (CNVs) and parental willingness for invasive prenatal diagnosis in a Chinese prenatal diagnosis center.

Methods

A total of 24,702 pregnant women were retrospectively analyzed at the Women and Children’s Hospital from January 2013 to April 2019, among which expanded NIPT had been successfully conducted in 24,702 pregnant women. The high-risk expanded NIPT results were validated by karyotype analysis and chromosomal microarray analysis. All the tested pregnant women were followed up for pregnancy outcomes.

Results

Of the 24,702 cases, successful follow-up was conducted in 98.77% (401/446) of cases with common trisomies and SCAs, 91.95% (80/87) of RAT and CNV cases, and 76.25% (18,429/24,169) of cases with low-risk screening results. The sensitivity of expanded NIPT was 100% (95% confidence interval[CI], 97.38–100%), 96.67%(95%CI, 82.78–99.92%), and 100%(95%CI, 66.37–100.00%), and the specificity was 99.92%(95%CI, 99.87–99.96%), 99.96%(95%CI, 99.91–99.98%), and 99.88% (95%CI, 99.82–99.93%) for the detection of trisomies 21, 18, and 13, respectively. Expanded NIPT detected 45,X, 47,XXX, 47,XXY, XYY syndrome, RATs, and CNVs with positive predictive values of 25.49%, 75%, 94.12%, 76.19%, 6.45%, and 50%, respectively. The women carrying fetuses with Trisomy 21/Trisomy 18/Trisomy 13 underwent invasive prenatal diagnosis and terminated their pregnancies at higher rates than those at high risk for SCAs, RATs, and CNVs.

Conclusions

Our study demonstrates that the expanded NIPT detects fetal trisomies 21, 18, and 13 with high sensitivity and specificity. The accuracy of detecting SCAs, RATs, and CNVs is still relatively poor and needs to be improved. With a high-risk expanded NIPT result, the women at high risk for common trisomies are more likely to undergo invasive prenatal diagnosis procedures and terminate their pregnancies than those with unusual chromosome abnormalities.
CircPTPRA blocks the recognition of RNA N6-methyladenosine through interacting with IGF2BP1 to suppress bladder cancer progression
Authors: Xie Fei , Huang Chao , Liu Feng , Zhang Hui , Xiao Xingyuan , Sun Jiayin , Zhang Xiaoping , Jiang Guosong
Published: April 2021

Background

Circular RNAs (circRNAs) have been found to have significant impacts on bladder cancer (BC) progression through various mechanisms. In this study, we aimed to identify novel circRNAs that regulate the function of IGF2BP1, a key m6A reader, and explore the regulatory mechanisms and clinical significances in BC.

Methods

Firstly, the clinical role of IGF2BP1 in BC was studied. Then, RNA immunoprecipitation sequencing (RIP-seq) analysis was performed to identify the circRNAs interacted with IGF2BP1 in BC cells. The overall biological roles of IGF2BP1 and the candidate circPTPRA were investigated in both BC cell lines and animal xenograft studies. Subsequently, we evaluated the regulation effects of circPTPRA on IGF2BP1 and screened out its target genes through RNA sequencing. Finally, we explored the underlying molecular mechanisms that circPTPRA might act as a blocker in recognition of m6A.

Results

We demonstrated that IGF2BP1 was predominantly binded with circPTPRA in the cytoplasm in BC cells. Ectopic expression of circPTPRA abolished the promotion of cell proliferation, migration and invasion of BC cells induced by IGF2BP1. Importantly, circPTPRA downregulated IGF2BP1-regulation of MYC and FSCN1 expression via interacting with IGF2BP1. Moreover, the recognition of m6A-modified RNAs mediated by IGF2BP1 was partly disturbed by circPTPRA through its interaction with KH domains of IGF2BP1.

Conclusions

This study identifies exonic circular circPTPRA as a new tumor suppressor that inhibits cancer progression through endogenous blocking the recognition of IGF2BP1 to m6A-modified RNAs, indicating that circPTPRA may serve as an exploitable therapeutic target for patients with BC.
Association of gravity drainage and complications following Whipple: an analysis of the ACS-NSQIP targeted database
Authors: Hall Bradley R. , Egr Zachary H. , Krell Robert W. , Padussis James C. , Shostrom Valerie K. , Are Chandrakanth , Reames Bradley N.
Published: April 2021

Background

The optimal type of operative drainage following pancreaticoduodenectomy (PD) remains unclear. Our objective is to investigate risk associated with closed drainage techniques (passive [gravity] vs. suction) after PD.

Methods

We assessed operative drainage techniques utilized in patients undergoing PD in the ACS-NSQIP pancreas-targeted database from 2016 to 2018. Using multivariable logistic regression to adjust for characteristics of the patient, procedure, and pancreas, we examined the association between use of gravity drainage and postoperative outcomes.

Results

We identified 9665 patients with drains following PD from 2016 to 2018, of which 12.7% received gravity drainage. 61.0% had a diagnosis of adenocarcinoma or pancreatitis, 26.5% had a duct <3 mm, and 43.5% had a soft or intermediate gland. After multivariable adjustment, gravity drainage was associated with decreased rates of postoperative pancreatic fistula (odds ratio [OR] 0.779, 95% confidence interval [CI] 0.653–0.930, p=0.006), delayed gastric emptying (OR 0.830, 95% CI 0.693–0.988, p=0.036), superficial SSI (OR 0.741, 95% CI 0.572–0.959, p=0.023), organ space SSI (OR 0.791, 95% CI 0.658–0.951, p=0.012), and readmission (OR 0.807, 95% CI 0.679–0.958, p=0.014) following PD.

Conclusions

Gravity drainage is independently associated with decreased rates of CR-POPF, DGE, SSI, and readmission following PD. Additional prospective research is necessary to better understand the preferred drainage technique following PD.
The prevention of – and first response to – injuries in Nepal: a review of policies and legislation
Authors: Pant Puspa Raj , Mytton Julie , Dharel Milan Raj , Dangi Amrit , Rai Writu Bhatta , Joshi Sunil Kumar
Published: April 2021

Background

Injuries, the cause of an estimated 4.5 million deaths annually and many more disabilities worldwide each year, are the predictable outcome of particular circumstances. One of the most effective ways to prevent injuries is through policy and legislation. The aim of this research study was to identify and critically review all policy and legislation in Nepal that had the potential to prevent injuries.

Methods

We identified legislation and policy that met inclusion criteria through a stakeholder meeting, networks and contacts, and websites and electronic resources. Each included document was critically reviewed to identify areas of strength and opportunities for improvement. We compared the included documents against WHO’s recommendations of known effective interventions.

Results

Sixty-two documents met the inclusion criteria for this review. Of these, 24 (38.7%) were exclusively related to road injuries, 11 (17.7%) to occupational injuries, 6 (9.7%) to injuries in the home and 5 (8.1%) to injuries at school; 30 (48.4%) documents included text related to the first response to injuries. Of 127 strategic recommendations by WHO that provided an area for policy or legislative focus, 21 (16.5%) were considered adequately met by Nepali policy and legislation, 43 (33.9%) were considered partially met and 63 (49.6%) were not met.

Conclusion

We drew five conclusions from this critical policy review, which we have related to recommendations as follows: widening the scope of legislation and policy for injury prevention to emphasize injuries occurring at home or school; addressing the causes of injuries and promoting proven preventive measures; greater clarity on both individual and institutional roles and responsibilities; trustworthy data and quality evidence to inform decision-making; and financial investment and capacity-strengthening for injury prevention and first response. The current system of federal governance in Nepal has potential for strengthening injury prevention and first response at the central, provincial and local levels.
TNF-α acutely enhances acid-sensing ion channel currents in rat dorsal root ganglion neurons via a p38 MAPK pathway
Authors: Wei Shuang , Qiu Chun-Yu , Jin Ying , Liu Ting-Ting , Hu Wang-Ping
Published: April 2021

Background

Tumor necrosis factor-α (TNF-α) is a pro-inflammatory cytokine involved in pain processing and hypersensitivity. It regulates not only the expression of a variety of inflammatory mediators but also the functional activity of some ion channels. Acid-sensing ion channels (ASICs), as key sensors for extracellular protons, are expressed in nociceptive sensory neurons and contribute to pain signaling caused by tissue acidosis. It is still unclear whether TNF-α has an effect on functional activity of ASICs. Herein, we reported that a brief exposure of TNF-α acutely sensitized ASICs in rat dorsal root ganglion (DRG) neurons.

Methods

Electrophysiological experiments on rat DRG neurons were performed in vitro and acetic acid induced nociceptive behavior quantified in vitro.

Results

A brief (5min) application of TNF-α rapidly enhanced ASIC-mediated currents in rat DRG neurons. TNF-α (0.1-10 ng/ml) dose-dependently increased the proton-evoked ASIC currents with an EC50 value of 0.12 ± 0.01 nM. TNF-α shifted the concentration-response curve of proton upwards with a maximal current response increase of 42.34 ± 7.89%. In current-clamp recording, an acute application of TNF-α also significantly increased acid-evoked firing in rat DRG neurons. The rapid enhancement of ASIC-mediated electrophysiological activity by TNF-α was prevented by p38 mitogen-activated protein kinase (MAPK) inhibitor SB202190, but not by non-selective cyclooxygenase inhibitor indomethacin, suggesting that p38 MAPK is necessary for this enhancement. Behaviorally, TNF-α exacerbated acid-induced nociceptive behaviors in rats via activation of local p38 MAPK pathway.

Conclusions

These results suggest that TNF-α rapidly enhanced ASIC-mediated functional activity via a p38 MAPK pathway, which revealed a novel peripheral mechanism underlying TNF-α involvement in rapid hyperalgesia by sensitizing ASICs in primary sensory neurons.
Feasibility and preliminary efficacy of a combined virtual reality, robotics and electrical stimulation intervention in upper extremity stroke rehabilitation
Authors: Norouzi-Gheidari Nahid , Archambault Philippe S. , Monte-Silva Katia , Kairy Dahlia , Sveistrup Heidi , Trivino Michael , Levin Mindy F. , Milot Marie-Hélène
Published: April 2021

Background

Approximately 80% of individuals with chronic stroke present with long lasting upper extremity (UE) impairments. We designed the perSonalized UPper Extremity Rehabilitation (SUPER) intervention, which combines robotics, virtual reality activities, and neuromuscular electrical stimulation (NMES). The objectives of our study were to determine the feasibility and the preliminary efficacy of the SUPER intervention in individuals with moderate/severe stroke.

Methods

Stroke participants (n = 28) received a 4-week intervention (3 × per week), tailored to their functional level. The functional integrity of the corticospinal tract was assessed using the Predict Recovery Potential algorithm, involving measurements of motor evoked potentials and manual muscle testing. Those with low potential for hand recovery (shoulder group; n = 18) received a robotic-rehabilitation intervention focusing on elbow and shoulder movements only. Those with a good potential for hand recovery (hand group; n = 10) received EMG-triggered NMES, in addition to robot therapy. The primary outcomes were the Fugl-Meyer UE assessment and the ABILHAND assessment. Secondary outcomes included the Motor Activity Log and the Stroke Impact Scale.

Results

Eighteen participants (64%), in either the hand or the shoulder group, showed changes in the Fugl-Meyer UE or in the ABILHAND assessment superior to the minimal clinically important difference.

Conclusions

This indicates that our personalized approach is feasible and may be beneficial in improving UE function in individuals with moderate to severe impairments due to stroke.

Trial registration

ClinicalTrials.gov NCT03903770. Registered 4 April 2019. Registered retrospectively.
The use of game modes to promote engagement and social involvement in multi-user serious games: a within-person randomized trial with stroke survivors
Authors: Pereira Fábio , Bermúdez i Badia Sergi , Jorge Carolina , Cameirão Mónica S.
Published: April 2021

Background

Serious games are promising for stroke rehabilitation, with studies showing a positive impact on reducing motor and cognitive deficits. However, most of the evidence is in the context of single-user rehabilitation, and little is known concerning the impact in multi-user settings. This study evaluates the impact that different game modes can have on engagement and social involvement during a two-user game. Specifically, we want to understand the benefits of game modalities based on competition, co-activation, and collaboration and analyze the influence of different motor and cognitive deficits and personality traits.

Methods

We developed a two-player setup—using tangible objects and a large screen interactive table—for upper limb rehabilitation purposes. We implemented a game that, while keeping the same basic mechanics, can be played in the three different modes (Competitive, Co-active, and Collaborative). We ran a within-person randomized study with 21 stroke survivors that were paired and played the game in its three versions. We used the Game Experience Questionnaire—Core Module to assess engagement and the Social Presence Module to assess Social Involvement. For personality, motor, and cognitive function, users answered the International Personality Item Pool (short version), Fugl-Meyer Assessment—Upper Extremity, Modified Ashworth Scale, and Montreal Cognitive Assessment, respectively.

Results

The Collaborative mode promoted significantly more Behavioral Involvement. The Competitive mode promoted more Flow and Challenge than the Co-active mode with participants with better cognitive performance, with low extraversion, or with higher motor skills. Participants with higher cognitive deficits reported more Competence with the Co-active mode.

Conclusions

Our results indicate that, for multi-user motor rehabilitation settings, the collaborative mode is the more appropriate gaming approach to promote social involvement, showing a high potential for increasing adherence and effectiveness of therapy. Additionally, we show that a player's motor and cognitive ability and personality should be considered when designing personalized tasks for multiplayer settings.
Why is repositioning public health innovation towards a social paradigm necessary? A reflection on the field of public health through the examples of Ebola and Covid-19
Authors: Niang Marietou , Dupéré Sophie , Alami Hassane , Gagnon Marie-Pierre
Published: April 2021

Health innovations are generally oriented on a techno-economic vision. In this perspective, technologies are seen as an end in themselves, and there is no arrangement between the technical and the social values of innovation. This vision prevails in sanitary crises, in which management is carried out based on the search for punctual, reactive, and technical solutions to remedy a specific problem without a systemic/holistic, sustainable, or proactive approach. This paper attempts to contribute to the literature on the epistemological orientation of innovations in the field of public health. Taking the Covid-19 and Ebola crises as examples, the primary objective is to show how innovation in health is oriented towards a techno-economic paradigm. Second, we propose a repositioning of public health innovation towards a social paradigm that will put more emphasis on the interaction between social and health dimensions in the perspective of social change. We will conclude by highlighting the roles that public health could play in allowing innovations to have more social value, especially during sanitary crises.
A modified anterior drawer test for anterior cruciate ligament ruptures
Authors: Zhao Guang-lei , Lyu Jin-yang , Liu Chang-quan , Wu Jian-guo , Xia Jun , Huang Gang-yong
Published: April 2021

Objective

This study was aimed to utilize a modified anterior drawer test (MADT) to detect the anterior cruciate ligament (ACL) ruptures and investigate its accuracy compares with three traditional tests.

Methods

Four hundred patients were prospectively enrolled between January 2015 and September 2017 preoperatively to undergo knee arthroscopic surgeries. The MADT, anterior drawer test, Lachman test, and pivot shift test were used in the outpatient clinical setting and were compared statistically for their accuracy in terms of ACL ruptures, with arthroscopic findings as the gold standard.

Results

The prevalence of ACL ruptures in this study was 37.0%. The MADT demonstrated the highest sensitivity (0.89) and accuracy (0.92) among the four tests and had comparable specificity (0.94) and a positive predictive value (0.90) compared with the anterior drawer test, Lachman test, and pivot shift test. The diagnostic odds ratio (DOR) of MADT was 122.92, with other test values of no more than 55.45. The area under the receiver operating characteristic curve (AUC) for the MADT was 0.92 ± 0.01, with a significant difference compared with that for the anterior drawer test (z= 17.00,p< 0.001), Lachman test (z= 9.66,p= 0.002), and pivot shift test (z = 16.39,p< 0.001). The interobserver reproducibility of the MADT was good, with a kappa coefficient of 0.86.

When diagnosing partial tears of ACL, the MADT was significantly more sensitive than the anterior drawer test (p< 0.001), Lachman test (p= 0.026), and pivot shift test (p= 0.013). The MADT showed similar sensitivity in detecting anteromedial and posterolateral bundle tears (p= 0.113) and no difference in diagnosing acute and chronic ACL ruptures (χ2= 1.682,p= 0.195).

Conclusions

The MADT is also an alternative diagnostic test to detect ACL tear, which is equally superior to the anterior drawer test, Lachman test, and pivot shifting test. It could improve the diagnosis of ACL ruptures combined with other clinical information including injury history, clinical examination, and radiological findings.

Levels of evidence

Level II/observational diagnostic studies

Trial registration

Chinese Clinical Trial Registry.ChiCTR1900022945/retrospectively registered
Efficacy of computed tomography-assisted limited decompression in the surgical management of thoracolumbar fractures with neurological deficit
Authors: Shi Landa , Chou Dean , Wang Yuqiang , Alizada Mirwais , Liu Yilin
Published: April 2021

Objective

To investigate the effect of CT-assisted limited decompression in managing single segment A3 lumbar burst fracture.

Method

A retrospective study (January 2015–June, 2019). One hundred six cases with single-level Magerl type A3 lumbar burst fractures treated with short-segment posterior internal fixation and limited decompression. Patients were divided into two groups: CT-assisted group and non-CT-assisted group. Perioperative factors, clinical outcomes, post-operative complications, imaging parameters, and health-related quality of life (HRQoL) were evaluated.

Results

Kyphosis, loss of anterior and posterior vertebral body heights, operative time, and post-operative complications were not significantly different between the two groups. The visual analog score (VAS) and spinal canal encroachment in the CT-assisted group were lower compared with the non-CT-assisted group (p < 0.05). The Japanese Orthopaedic Association (JOA) score, the simplified HRQoL scale, and the American Spinal Injury Association (ASIA) Spinal Cord Injury Grade in the CT-assisted group were significantly higher compared with the non-CT-assisted group (p < 0.05).

Conclusion

CT-assisted limited decompression in the treatment of single-segment A3 lumbar burst fracture can achieve better fracture reduction and surgical results and improve the long-term recovery of the patients’ neurological function and quality of life.
Application of a simple skin stretching system and negative pressure wound therapy in repair of complex diabetic foot wounds
Authors: Wu Yaojun , Chen Liang , Wu Shaokun , Yu Liying , Chen Mimi , Wang Jingnan , Chen Jiejie , Pang Qingjiang
Published: April 2021

The management of complex diabetic foot wounds with large skin defects poses a challenge for surgeons. We presented a simple skin stretching system and negative pressure wound therapy for the repair of complex diabetic foot wounds to examine the effectiveness and safety.

A total of 16 patients with diabetic foot ulcers were retrospectively reviewed between January 2015 and October 2020. All patients underwent the treatment by 3 stages. In stage 2, these difficult-to-close wounds of diabetes foot were residual. This method was applied to the wounds with a median defect size of 20.42 cm2(range, 4.71–66.76 cm2).

The median time for closure of complex diabetic foot wounds was 14 days ranging from 8 to 19 days. With respect to the absolute rates of reduction, it was observed with a median of 1.86 cm2/day, ranging from 0.29 cm2/day to 8.35 cm2/day. In accordance with the localization of the defect, the patients were divided into 3 groups: side of the foot (37.5%), dorsum of the foot (50.0%), and others (12.5%). There was no statistical difference between side of the foot and dorsum of the foot in terms of the median defect size withP= 0.069 (Kruskal–Wallis test). Otherwise, there were statistically significant differences regarding the median time and the median absolute rates (P< 0.05; Kruskal–Wallis test). No severe complications were encountered in this study.

In summary, our results show that application of the simple skin stretching system and NPWT is an effective and safe approach to complex diabetic foot wounds. Nevertheless, more attention should be paid to the appropriate patient selection and intraoperative judgment to ensure wound closure and avoid undue complications.
Development of a tibial experimental non-union model in rats
Authors: Wu Xue-Qiang , Wang Dong , Liu Yang , Zhou Jun-Lin
Published: April 2021

Background

Many non-union animal models have been developed to explore the problems surrounding fracture healing. However, the existing models are not perfect and cannot satisfy all non-union studies. This study aimed to make a non-union model of the tibia in rats by cauterization of the posterior of 2 mm on both sides of the fracture end after open osteotomy of the tibia and fixing the fractured tibia with a Kirschner wire 0.8 mm in diameter.

Methods

For this study, 96 female adult Sprague-Dawley (SD) rats were used. The rats underwent surgery to produce a tibial open fracture and were fixed with a 0.8-mm diameter Kirschner wire. In 48 of the rats, the periosteum proximal and distal to the fracture end was cauterized.

Results

At 2, 4, 6, and 8 weeks after surgery, radiological and histological analysis showed typical physiological healing in the control group, and the healing rate was 100% at 6 weeks. But the non-union group was characterized by resorption of the fracture ends with few callus formations and no bridging callus formation, and the healing rate was 0% at 8 weeks.

Conclusions

This method represents a reproducible model to create atrophic non-unions. This model provides a new option for studying the basic healing mechanisms and evaluating new therapies for bone regeneration and treatment of non-unions.
The effectiveness and safety of LMWH for preventing thrombosis in patients with spinal cord injury: a meta-analysis
Authors: Lin Ze , Sun Yun , Xue Hang , Chen Lang , Yan Chenchen , Panayi Adriana C. , Mi Bobin , Liu Guohui
Published: April 2021

Background

Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are commonly used for preventing venous thrombosis of the lower extremity in patients with traumatic spinal cord injury. Although, LMWH is the most commonly used drug, it has yet to be established whether it is more effective and safer than UFH. Further, a comparison of the effectiveness of LMWH in preventing thrombosis at different locations and different degrees of spinal cord injury has also not been clearly defined.

Materials and methods

Cohort studies comparing the use of LMWH and UFH in the prevention of lower limb venous thrombosis in patients with spinal cord injury were identified using PubMed. The risk of bias and clinical relevance of the included studies were assessed using forest plots. The Newcastle-Ottawa quality assessment scale was used to evaluate the quality of the included studies. The main results of the study were analyzed using Review Manager 5.3.

Results

A total of five studies were included in this meta-analysis. Four studies compared the effectiveness and safety of LMWH and UFH in preventing thrombosis in patients with spinal cord injury. No significant differences were found between the therapeutic effects of the two drugs, and the summary RR was 1.33 (95% CI 0.42–4.16; P = 0.63). There was also no significant difference in the risk of bleeding between the two medications, and the aggregate RR was 0.78 (95% CI 0.55–1.12; P = 0.18). When comparing the efficacy of LMWH in preventing thrombosis in different segments and different degrees of spinal cord injury, no significant differences were found.

Conclusions

The results of this analysis show that compared with UFH, LMWH has no obvious advantages in efficacy nor risk prevention, and there is no evident difference in the prevention of thrombosis for patients with injuries at different spinal cord segments.
Clinical features and disease severity in patients with mosaic neurofibromatosis type 1: a single-center study and literature review
Authors: Ejerskov C. , Raundahl M. , Gregersen P. A. , Handrup M. M.
Published: April 2021

Background

The mosaic form of neurofibromatosis type 1 (NF1) is called mosaic NF1 (MNF1). No specific MNF1 follow-up guidelines exist. It is debatable if patients with MNF1 should be clinically examined and undergo follow-up in accordance with the standard NF1 guidelines, as MNF1 patients more often may develop more benign phenotypes and thereby less disease-associated complications including cognitive impairment. We discussed the need for a specific MNF1 follow-up guideline with focus on frequency of plexiform neurofibromas and NF1-associated complications.

Method

A systematic retrospective data collection in a MNF1 cohort from one of two Danish national centers of NF1 Expertise was completed. Data collected included demographics, clinical features including NF1 diagnostic criteria and NF1-associated complications. Recent literature in the field was reviewed.

Results

We identified 17 patients with MNF1 with a median age of 37 years [4; 66]. Eleven (65%) were females. Five patients (30%) had a plexiform neurofibroma. The median age at detection of plexiform neurofibroma was 30 years [14; 60]. Nine (53%) had at least one NF1-related complication; scoliosis, hypertension, ADHD, learning disability, language delay, autism and delay in gross and fine motor function development. We reviewed nine articles. In total, 126 cases were described within three case-series. Nineteen (15%) had a plexiform neurofibroma and in total, 23 NF1-associated complications were reported including language delay, learning disability and skeletal abnormalities. Furthermore, from the literature it was evident that the diagnosing of MNF1 varies among physicians and across countries.

Conclusion

Patients with MNF1 present with plexiform neurofibromas and other NF1-related complications with a frequency requiring that follow-up of MNF1 patients should be in accordance with the standard NF1 guideline in both childhood and adulthood. Physicians should be aware of cognitive impairment as a complication to MNF1. To develop a specific MNF1 follow-up guideline, there is a need for an international consensus on the diagnostic criteria for MNF1 and a follow-up study conducted in a larger MNF1 cohort.
Coupling sparse Cox models with clustering of longitudinal transcriptomics data for trauma prognosis
Authors: Constantino Cláudia S. , Carvalho Alexandra M. , Vinga Susana
Published: April 2021

Background

Longitudinal gene expression analysis and survival modeling have been proved to add valuable biological and clinical knowledge. This study proposes a novel framework to discover gene signatures and patterns in a high-dimensional time series transcriptomics data and to assess their association with hospital length of stay.

Methods

We investigated a longitudinal and high-dimensional gene expression dataset from 168 blunt-force trauma patients followed during the first 28 days after injury. To model the length of stay, an initial dimensionality reduction step was performed by applying Cox regression with elastic net regularization using gene expression data from the first hospitalization days. Also, a novel methodology to impute missing values to the genes selected previously was proposed. We then applied multivariate time series (MTS) clustering to analyse gene expression over time and to stratify patients with similar trajectories. The validation of the patients’ partitions obtained by MTS clustering was performed using Kaplan-Meier curves and log-rank tests.

Results

We were able to unravel 22 genes strongly associated with hospital’s discharge. Their expression values in the first days after trauma showed to be good predictors of the length of stay. The proposed mixed imputation method allowed to achieve a complete dataset of short time series with a minimum loss of information for the 28 days of follow-up. MTS clustering enabled to group patients with similar genes trajectories and, notably, with similar discharge days from the hospital. Patients within each cluster have comparable genes’ trajectories and may have an analogous response to injury.

Conclusion

The proposed framework was able to tackle the joint analysis of time-to-event information with longitudinal multivariate high-dimensional data. The application to length of stay and transcriptomics data revealed a strong relationship between gene expression trajectory and patients’ recovery, which may improve trauma patient’s management by healthcare systems. The proposed methodology can be easily adapted to other medical data, towards more effective clinical decision support systems for health applications.
Adherence to participant flow diagrams in trials on postoperative pain management after total hip and knee arthroplasty: a methodological review
Authors: Rønsbo Thea Nørgaard , Laigaard Jens , Pedersen Casper , Mathiesen Ole , Karlsen Anders Peder Højer
Published: April 2021

Background

The Consolidated Standards of Reporting Trials (CONSORT) statement aims to improve transparent reporting of randomised clinical trials. It comprises a participant flow diagram with the reporting of essential numbers for enrolment, allocation and analyses. We aimed to quantify the use of participant flow diagrams in randomised clinical trials on postoperative pain management after total hip and knee arthroplasty.

Methods

We searched PubMed, Embase and CENTRAL up till January 2020. The primary outcome was the proportion of trials with adequate reporting of participant flow diagrams, defined as reporting of number of participants screened for eligibility, randomised and included in the primary analysis. Secondary outcomes were recruitment (randomised:screened) and retention (analysed:randomised) rates, reporting of a statistical strategy, reasons for exclusion from the primary analysis and handling of missing outcome data. Trends over time were assessed with statistical process control.

Results

Of the 570 included trials, we found adequate reporting in 240 (42%). Reporting with participant flow diagram increased significantly over time. Median recruitment was 73% (IQR 44–91%), and retention was 97% (IQR 93–100%). These rates did not change over time. Trials with adequate reporting of participant flow were more likely to report a statistical strategy (41% vs 8%), reasons for post-randomisation exclusions (100% vs 55%) and handling of missing outcome data (14% vs 6%).

Conclusions

Adherence to participant flow diagrams for RCTs has increased significantly over time. Still, there is room for improvement of adequate reporting of flow diagrams, to increase transparency of trials details.
Bedside Ultrasound Conducted in Kids with distal upper Limb fractures in the Emergency Department (BUCKLED): a protocol for an open-label non-inferiority diagnostic randomised controlled trial
Authors: Snelling Peter J. , Keijzers Gerben , Byrnes Joshua , Bade David , George Shane , Moore Mark , Jones Philip , Davison Michelle , Roan Rob , Ware Robert S.
Published: April 2021

Background

Children frequently present to the emergency department (ED) with forearm injuries and often have x-rays to determine if there is a fracture. Bedside ultrasound, also known as point-of-care ultrasound (POCUS), is an alternative diagnostic test used to rapidly diagnose a fracture at the time of examination, without exposing children to ionising radiation. Prospective studies have demonstrated high agreement between POCUS and x-ray findings. However, whether the initial imaging modality affects the patient’s medium-term physical function is unknown.

Methods

This is a multicentre, open-label, non-inferiority randomised controlled trial conducted in Australian EDs. Recruitment will continue until 112 children with distal forearm injuries (including 48 buckle fractures) per trial arm have achieved the primary outcome measure. Patients aged 5–15 years presenting with an isolated, acute, clinically non-angulated, distal forearm injury with suspected fracture will have their initial diagnostic approach randomised to either POCUS, performed by a credentialled practitioner, or x-ray imaging. If a cortical breach fracture is identified on POCUS, the patient will receive x-rays and have usual care. If a buckle fracture is identified, the patient will have their forearm placed in a splint and be discharged home. Patients will be followed up at 1, 4 and 8 weeks. The primary outcome is upper limb physical function at 4 weeks, as determined by the Pediatric Upper Extremity Short Patient-Reported Outcomes Measurement Information System (PROMIS) tool. Secondary outcomes include healthcare costs, satisfaction, pain, complications, rates of imaging, ED length of stay and diagnostic accuracy.

Discussion

If POCUS is non-inferior to x-ray in terms of patient’s medium-term physical function, it may have an effect on overall health care resource use, including the number of x-ray performed and earlier ED discharge. Although prospective studies have confirmed the accuracy of POCUS, this will be the first RCT to assess non-inferiority of functional outcomes of POCUS to diagnose non-angulated paediatric distal forearm injuries, compared to x-ray. POCUS may be of particular importance in settings where access to x-ray imaging can be limited either during or after-hours, as it can aid the triaging and management of patients.

Trial registration

Prospectively registered with the ANZCTR on 29 May 2020 (ACTRN12620000637943).
Colorectal cancer and Blastocystis sp. infection
Authors: Sulżyc-Bielicka Violetta , Kołodziejczyk Lidia , Adamska Małgorzata , Skotarczak Bogumiła , Jaczewska Sylwia , Safranow Krzysztof , Bielicki Paweł , Kładny Józef , Bielicki Dariusz
Published: April 2021

Background

Blastocystis sp. is a common intestinal protozoan found worldwide. Based on gene analysis, 17 subtypes (STs, ST1–ST17) have been identified, 9 of which have been isolated from humans. Differences in clinical consequences may depend on differences among the STs. Here, we evaluated the prevalence of Blastocystis sp. in patients with colorectal cancer (CRC) compared to a control group and assessed the relationships between Blastocystis sp. infection and sex; age; and CRC grade, stage, and location.

Methods

The study included 107 CRC patients (41 women and 66 men, median age 65 years); 124 subjects without colorectal cancer or a history of oncological disease comprised the control group (55 women and 69 men, median age 63). Stool samples were collected from patients before oncological treatment and examined using light microscopy (iodine-stained smear). Additionally, PCR-based identification of Blastocystis sp. was performed in 95 stool samples from CRC patients and 76 stool samples from the control group.

Results

Light microscopy showed that the prevalence of Blastocystis sp. was significantly higher in CRC patients than in the control group (12.15% and 2.42%, respectively; p = 0.0041). Multivariate analysis showed that the odds of Blastocystis sp. infection were fivefold higher in the CRC group than in the control group. PCR-based molecular examinations demonstrated that the proportion of patients infected with Blastocystis sp. was significantly higher in the CRC group than in the control group (12.63% and 2.63%, respectively; p = 0.023). The predominant ST in the CRC group was ST3, detected in nine patients (75%), followed by ST1 (2 patients, 16.7%) and ST2 (1 patient, 8.3%). No association was found between Blastocystis sp. infection and age, sex, or CRC stage, grade, or location.

Conclusions

The results showed that CRC was associated with an increased risk of opportunistic Blastocystis sp. infection, even before oncological treatment. To the best of our knowledge, this is the first report estimating the prevalence of Blastocystis sp. infection in CRC patients before oncological treatment in Europe.
Molecular analysis suggests that Namibian cheetahs (Acinonyx jubatus) are definitive hosts of a so far undescribed Besnoitia species
Authors: Schares Gereon , Joeres Maike , Rachel Franziska , Tuschy Mareen , Czirják Gábor Á. , Maksimov Pavlo , Conraths Franz J. , Wachter Bettina
Published: April 2021

Background

Besnoitia darlingi,B. neotomofelisandB. oryctofelisiare closely related coccidian parasites with felids as definitive hosts. These parasites use a variety of animal species as intermediate hosts. North American opossums (Didelphis virginiana), North American southern plains woodrats (Neotoma micropus) and South American domestic rabbits (Oryctolagus cuniculus) are intermediate hosts ofB. darlingi,B. neotomofelisandB. oryctofelisi, respectively. Based on conserved regions in the internal transcribed spacer-1 (ITS1) sequence of the ribosomal DNA (rDNA), a real-time PCR for a sensitive detection of theseBesnoitiaspp. in tissues of intermediate hosts and faeces of definitive hosts has recently been established. Available sequence data suggest that species such asB. akodoniandB. jellisoniare also covered by this real-time PCR. It has been hypothesised that additionalBesnoitiaspp. exist worldwide that are closely related toB. darlingiorB. darlingi-like parasites (B. neotomofelis,B. oryctofelisi,B. akodoniorB. jellisoni). Also related, but not as closely, isB. besnoiti, the cause of bovine besnoitiosis.

Methods

Faecal samples from two free-ranging cheetahs (Acinonyx jubatus) from Namibia that had previously tested positive for coccidian parasites by coproscopy were used for this study. A conventional PCR verified the presence of coccidian parasite DNA. To clarify the identity of these coccidia, the faecal DNA samples were further characterised by species-specific PCRs and Sanger sequencing.

Results

One of the samples tested positive forB. darlingiorB. darlingi-like parasites by real-time PCR, while no other coccidian parasites, includingToxoplasma gondii,Hammondia hammondi,H. heydorni,B. besnoitiandNeospora caninum, were detected in the two samples. The rDNA of theB. darlingi-like parasite was amplified and partially sequenced. Comparison with existing sequences in GenBank revealed a close relationship to otherBesnoitiaspp., but also showed clear divergences.

Conclusions

Our results suggest that a so far unknownBesnoitiaspecies exists in Namibian wildlife, which is closely related toB. darlingi,B. neotomofelis,B. oryctofelisi,B. akodoniorB. jellisoni.The cheetah appears to be the definitive host of this newly discovered parasite, while prey species of the cheetah may act as intermediate hosts.

Graphical Abstract
Intensity and mechanisms of deltamethrin and permethrin resistance in Anopheles gambiae s.l. populations in southern Benin
Authors: Sagbohan Hermann Watson , Kpanou Casimir D. , Osse Razaki , Dagnon Fortuné , Padonou Germain G. , Sominahouin André Aimé , Salako Albert Sourou , Sidick Aboubakar , Sewade Wilfried , Akinro Bruno , Ahmed Saadani , Impoinvil Daniel , Agbangla Clément , Akogbeto Martin
Published: April 2021

Background

Insecticide resistance is threatening the effectiveness of efforts to control malaria vectors in Benin. This study explores the levels and mechanisms of insecticide resistance in An. gambiae s.l. to pyrethroids.

Methods

Larvae were collected from August 2017 to July 2018 in five communes in southern Benin (Adjohoun, Allada, Bohicon, Cotonou, and Porto-Novo) representing diverse ecological regions, and were reared in Benin’s insectary. Two- to five-day-old female mosquitoes from each district were exposed to multiple doses of deltamethrin and permethrin (1×, 2×, 5×, and 10×) using the WHO insecticide resistance intensity bioassay. The effect of pre-exposure to the synergist, piperonyl butoxide (PBO), was also tested at different pyrethroid doses. Molecular allele frequencies of kdr (1014F) and ace-1R (119S) insecticide resistance mutations and levels of detoxification enzymes were determined for mosquitoes sampled from each study area.

Results

An. gambiae s.l. were resistant to pyrethroid-only exposure up to 10× the diagnostic doses in all the study sites for both deltamethrin and permethrin. Mortality was significantly higher in An. gambiae s.l. pre-exposed to PBO followed by exposure to deltamethrin or permethrin compared to mosquitoes exposed to deltamethrin or permethrin only (p < 0.001). The difference in mortality between deltamethrin only and PBO plus deltamethrin was the smallest in Cotonou (16–64%) and the greatest in Bohicon (12–93%). The mortality difference between permethrin only and PBO plus permethrin was the smallest in Cotonou (44–75%) and the greatest in Bohicon (22–72%). In all the study sites, the kdr resistance allele (1014F) frequency was high (75–100%), while the ace-1 resistance allele (G119S) frequency was low (0–3%). Analysis of the metabolic enzymatic activity of An. gambiae s.l. showed overexpression of nonspecific esterases and glutathione S-transferases (GST) in all study sites. In contrast to the PBO results, oxidase expression was low and was similar to the susceptible An. gambiae s.s. Kisumu strain in all sites.

Conclusion

There is high-intensity resistance to pyrethroids in southern Benin. However, pre-exposure to PBO significantly increased susceptibility to the pyrethroids in the different An. gambiae s.l. populations sampled. The use of PBO insecticide-treated bed nets may help maintain the gains in An. gambiae (s.l.) control in southern Benin.

Graphical Abstract
Emerging genetic complexity and rare genetic variants in neurodegenerative brain diseases
Authors: Perrone Federica , Cacace Rita , van der Zee Julie , Van Broeckhoven Christine
Published: April 2021

Knowledge of the molecular etiology of neurodegenerative brain diseases (NBD) has substantially increased over the past three decades. Early genetic studies of NBD families identified rare and highly penetrant deleterious mutations in causal genes that segregate with disease. Large genome-wide association studies uncovered common genetic variants that influenced disease risk. Major developments in next-generation sequencing (NGS) technologies accelerated gene discoveries at an unprecedented rate and revealed novel pathways underlying NBD pathogenesis. NGS technology exposed large numbers of rare genetic variants of uncertain significance (VUS) in coding regions, highlighting the genetic complexity of NBD. Since experimental studies of these coding rare VUS are largely lacking, the potential contributions of VUS to NBD etiology remain unknown. In this review, we summarize novel findings in NBD genetic etiology driven by NGS and the impact of rare VUS on NBD etiology. We consider different mechanisms by which rare VUS can act and influence NBD pathophysiology and discuss why a better understanding of rare VUS is instrumental for deriving novel insights into the molecular complexity and heterogeneity of NBD. New knowledge might open avenues for effective personalized therapies.