bluuebunny/crossref_metadata_2025 huggingface dataset:
Musculoskeletal Injury in Reserve Officers’ Training Corps: A Report From the Athletic Training Practice-Based Research Network
Authors: Radzak Kara N. , Sefton JoEllen M. , Timmons Mark K. , Lopp Rachel , Stickley Christopher D. , Lam Kenneth C.
Published: September 2020

Background:

Reserve Officers’ Training Corps (ROTC) cadets must meet the same physical standards as active duty military servicemembers and undergo organized physical training (PT). ROTC participation, like all physical activity, can result in training-related musculoskeletal injury (MSKI), and of course, cadets could sustain MSKI outside of ROTC. However, MSKI incidence in ROTC programs is largely unknown.

Purpose:

To describe patient and injury demographics of MSKI in 5 universities’ Army ROTC programs.

Study Design:

Descriptive epidemiology study.

Methods:

A retrospective chart review of electronic medical records was performed using the Athletic Training Practice-Based Research Network (AT-PBRN). Athletic trainers at 5 clinical practice sites within the AT-PBRN documented injury assessments via a web-based electronic medical record system. Medical records during the 2017-2018 and 2018-2019 academic years were used for analysis. Summary statistics were calculated for age, sex, height, body mass, military science year, training ability group, mechanism of injury, activity type associated with injury, anatomic location of injury, participation status, injury severity, and diagnosis.

Results:

A total of 364 unique injuries were documented. Cadets in the most advanced fitness group (Alpha; n = 148/364) and in their third year of training (n = 97/364) presented with the most injuries. Injuries most commonly occurred during PT (n = 165/364). Insidious onset (n = 146/364) and noncontact (n = 115/364) mechanisms of injury were prevalent. The most frequent anatomic location of injury was the knee (n = 71/364) followed by the ankle (n = 57/364). General sprain/strain was the most frequent International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code reported (n = 34/364).

Conclusion:

The knee was the most frequent location of MSKI in ROTC participants, and most MSKIs had insidious onset. Cadets with higher injury frequency were high achieving (Alpha) and in a critical time point in ROTC (military science year 3). The majority of MSKIs can be attributed to ROTC training, with PT being the most frequent activity associated with injury. Civilian health care providers, from whom ROTC cadets will most likely seek medical attention, need to be aware of ROTC physical demands as well as the characteristics of training-related injuries.
The Loop ’n’ Tack Knot: Biomechanical Analysis of a Novel Suture Technique for Proximal Biceps Tenodesis
Authors: Acosta Jonathan , Rinaldi John M. , Guth J. Jared , Akhavan Sam
Published: September 2020

Background:

Secure tendon grasping is critical to the success of any tenodesis procedure. Several techniques currently used for tendon grasping can result in longitudinal splitting of the tendon, causing construct failure and failure of the tenodesis.

Purpose:

To compare the Loop ’n’ Tack knot as a tendon-grasping technique with other common suture techniques. We investigated the biomechanical strength and mode of failure.

Study Design:

Controlled laboratory study.

Methods:

Eleven matched pairs of proximal biceps were harvested from fresh-frozen cadaveric shoulders. One tendon from each pair was stitched using 1 of 4 different techniques. The suture techniques evaluated included the Loop ’n’ Tack with 2 different types of high-strength nonabsorbable suture, a double half-racking stitch, and a Krakow stitch. Samples were cyclically loaded between 5 and 20 N for 100 cycles, followed by a pull to failure at 33 mm/s.

Results:

The Loop ’n’ Tack techniques were equivalent to the double half-racking and Krakow techniques for load to ultimate failure ( P = .817 and P = .984, respectively). The double half-racking technique was the stiffest construct, which was significantly greater than the second-stiffest group, the Loop ’n’ Tack method with both FiberLink suture ( P = .012) and SutureTape ( P = .002), which had greater stiffness than the Krakow group ( P < .001). The most common failure mode for the Loop ’n’ Tack stitch was suture breakage compared with the Krakow and double half-racking methods, where the most common mode of failure was suture pullout from the tendon ( P < .001).

Conclusion:

Biomechanical testing found that the Loop 'n’ Tack techniques had similar ultimate load to failure values when compared with the double half-racking and Krakow methods. Mode-of-failure analysis showed that the Loop 'n’ Tack construct typically failed by suture breakage, whereas the other techniques failed by suture pullout.

Clinical Relevance:

The Loop 'n’ Tack technique allows for secure grasping of tissue without the need for externalization of the tendon. This technique may be beneficial in compromised or poor-quality tissue without reducing overall pullout strength when compared with a standard half-racking or Krakow stitch.
Hierarchical siting of macro fire station and micro fire station
Authors: Yu Wenhao , Chen Yujie , Guan Menglin
Published: September 2020

With the rapid increase of city building density, public emergency service system for providing fire services faces increasing challenge in reducing the loss of lives and property, especially for the reduction of massive casualties in fire accidents. For obtaining a higher benefit from public service facilities, GIS-based techniques such as location optimization are commonly used. However, as a special facility, fire emergency facilities are quite particular in siting and providing services, and they have their unique demands including specific response time, benefit maximization, workload balancing and cost minimization; traditional optimization methods for fire facility siting are difficult to account for all of these objectives. Furthermore, the public emergency services agencies in China are implementing a plan to establish a hierarchical fire service system by siting fire stations with different capacities, and under this context, the general covering models with the same level of facilities are limited in their effectiveness. Therefore, this paper proposes a hierarchical covering model which takes into account the different characteristics of different levels of fire facilities (i.e. macro fire station and micro fire station). The case study of Nanjing city proves that our model is effective in practical applications of emergency services optimization.
The Platform Canvas—Conceptualization of a Design Framework for Multi-Sided Platform Businesses
Authors: Allweins Marcel M. , Proesch Markus , Ladd Ted
Published: September 2020

Digital multi-sided platforms reshape today’s economy by reducing coordination costs among participants in a market. The platform’s business model creates and captures value differently than a traditional linear business model. Just as the Business Model Canvas helps entrepreneurs and professionals visualize the essential elements and mechanisms of a linear business model, this paper proposes a Platform Canvas to diagram the essential elements of a multi-sided platform business, including the architectural relations of these elements and the dynamics of the network effect. We then describe how the Platform Canvas can be useful to entrepreneurs, educators and scholars.
F-actin Regulates Osteoblastic Differentiation of Mesenchymal Stem Cells on TiO2 Nanotubes Through MKL1 and YAP/TAZ
Authors: Tong Zhicheng , Liu Yanchang , Xia Runzhi , Chang Yongyun , Hu Yi , Liu Pengcheng , Zhai Zanjing , Zhang Jingwei , Li Huiwu
Published: September 2020

Titanium and titanium alloys are widely used in orthopedic implants. Modifying the nanotopography provides a new strategy to improve osseointegration of titanium substrates. Filamentous actin (F-actin) polymerization, as a mechanical loading structure, is generally considered to be involved in cell migration, endocytosis, cell division, and cell shape maintenance. Whether F-actin is involved and how it functions in nanotube-induced osteogenic differentiation of mesenchymal stem cells (MSCs) remain to be elucidated. In this study, we fabricated TiO2 nanotubes on the surface of a titanium substrate by anodic oxidation and characterized their features by scanning electron microscopy (SEM), X-ray energy dispersive analysis (EDS), and atomic force microscopy (AFM). Alkaline phosphatase (ALP) staining, Western blotting, qRT-PCR, and immunofluorescence staining were performed to explore the osteogenic potential, the level of F-actin, and the expression of MKL1 and YAP/TAZ. Our results showed that the inner diameter and roughness of TiO2 nanotubes increased with the increase of the anodic oxidation voltage from 30 to 70 V, while their height was 2 μm consistently. Further, the larger the tube diameter, the stronger the ability of TiO2 nanotubes to promote osteogenic differentiation of MSCs. Inhibiting F-actin polymerization by Cyto D inhibited osteogenic differentiation of MSCs as well as the expression of proteins contained in focal adhesion complexes such as vinculin (VCL) and focal adhesion kinase (FAK). In contrast, after Jasp treatment, polymerization of F-actin enhanced the expression of RhoA and transcription factors YAP/TAZ. Based on these data, we concluded that TiO2 nanotubes facilitated the osteogenic differentiation of MSCs, and this ability was enhanced with the increasing diameter of the nanotubes within a certain range (30–70 V). F-actin mediated this process through MKL1 and YAP/TAZ.
Major government customer and management earnings forecasts
Authors: Cheng Agnes C. S. , Huang Wenli , Zhang Shaojun
Published: September 2020

This paper examines whether customer base composition in the US, that is, whether a firm’s major customers are government entities or publicly traded companies, affects the properties of its management earnings forecasts (MEFs). Using a sample of 1168 MEFs from 1998 to 2014, we find that firms whose major customers are government entities (i.e., government suppliers) issue more precise and more accurate MEFs than firms whose major customers are public companies (i.e., corporate suppliers). Moreover, when managers disclose negative information to the market, earnings forecasts issued by government suppliers have greater price impact than those issued by corporate suppliers. Collectively, our empirical results suggest that having major government customers has a positive impact on the quality of MEFs.
Acupuncture attenuates the development of diabetic peripheral neuralgia by regulating P2X4 expression and inflammation in rat spinal microglia
Authors: Tang He-yong , Wang Fan-jing , Ma Jun-long , Wang Hao , Shen Guo-ming , Jiang Ai-juan
Published: September 2020

Diabetic peripheral neuropathy (DPN) is a chronic microvascular complication of diabetes. The purpose of this study is to find the underlying mechanism for the effects of acupuncture in DPN rats. Rats were rendered diabetic with a single injection of 35 mg/kg streptozotocin (STZ). These STZ-diabetic rats were treated with acupuncture for 20 min once daily. The therapeutic efficacy of acupuncture was assessed using mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) evaluations. After 14 days treatment, acupuncture markedly reduced the pathological injury in STZ-diabetic rats. Moreover, it significantly down-regulated P2X4 and OX42 expression along with the reduced levels of inflammatory factors (CXCR3, TNF-α, IL-1β, IL-6), GSP and lipid metabolisms in the spinal cord of the DPN rats. Acupuncture could relieve DPN in rats by regulating P2X4 expression and inflammation in spinal microglia.
Identification, characterization and functional analysis of AGAMOUS subfamily genes associated with floral organs and seed development in Marigold (Tagetes erecta)
Authors: Zhang Chunling , Wei Ludan , Wang Wenjing , Qi Wenquan , Cao Zhe , Li Hang , Bao Manzhu , He Yanhong
Published: September 2020

Background

AGAMOUS (AG) subfamily genes regulate the floral organs initiation and development, fruit and seed development. At present, there has been insufficient study of the function of AG subfamily genes in Asteraceae. Marigold (Tagetes erecta) belongs to Asteraceae family whose unique inflorescence structure makes it an important research target for understanding floral organ development in plants.

Results

Four AG subfamily genes of marigold were isolated and phylogenetically grouped into class C (TeAG1 and TeAG2) and class D (TeAGL11–1 and TeAGL11–2) genes. Expression profile analysis demonstrated that these four genes were highly expressed in reproductive organs of marigold. Subcellular localization analysis suggested that all these four proteins were located in the nucleus. Protein-protein interactions analysis indicated that class C proteins had a wider interaction manner than class D proteins. Function analysis of ectopic expression in Arabidopsis thaliana revealed that TeAG1 displayed a C function specifying the stamen identity and carpel identity, and that TeAGL11–1 exhibited a D function regulating seed development and petal development. In addition, overexpression of both TeAG1 and TeAGL11–1 leaded to curling rosette leaf and early flowering in Arabidopsis thaliana.

Conclusions

This study provides an insight into molecular mechanism of AG subfamily genes in Asteraceae species and technical support for improvement of several floral traits.
Modelling and predicting the spatio-temporal spread of COVID-19 in Italy
Authors: Giuliani Diego , Dickson Maria Michela , Espa Giuseppe , Santi Flavio
Published: September 2020

Background

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was first detected in China at the end of 2019 and it has since spread in few months all over the World. Italy was one of the first Western countries who faced the health emergency and is one of the countries most severely affected by the pandemic. The diffusion of Coronavirus disease 2019 (COVID-19) in Italy has followed a peculiar spatial pattern, however the attention of the scientific community has so far focussed almost exclusively on the prediction of the evolution of the disease over time.

Methods

Official freely available data about the number of infected at the finest possible level of spatial areal aggregation (Italian provinces) are used to model the spatio-temporal distribution of COVID-19 infections at local level. An endemic-epidemic time-series mixed-effects generalized linear model for areal disease counts has been implemented to understand and predict spatio-temporal diffusion of the phenomenon.

Results

Three subcomponents characterize the fitted model. The first describes the transmission of the illness within provinces; the second accounts for the transmission between nearby provinces; the third is related to the evolution of the disease over time. At the local level, the provinces first concerned by containment measures are those that are not affected by the effects of spatial neighbours. On the other hand, the component accounting for the spatial interaction with surrounding areas is prevalent for provinces that are strongly involved by contagions. Moreover, the proposed model provides good forecasts for the number of infections at local level while controlling for delayed reporting.

Conclusions

A strong evidence is found that strict control measures implemented in some provinces efficiently break contagions and limit the spread to nearby areas. While containment policies may potentially be more effective if planned considering the peculiarities of local territories, the effective and homogeneous enforcement of control measures at national level is needed to prevent the disease control being delayed or missed as a whole. This may also apply at international level where, as it is for the European Union or the United States, the internal border checks among states have largely been abolished.
Anti-Ma-associated paraneoplastic cerebellar degeneration in a patient with nodular lymphocyte-predominant Hodgkin lymphoma: a case report
Authors: Inui Ryoma , Saito Kenki , Shimomura Yoshimitsu , Yamashita Daisuke , Kawamoto Michi , Ishikawa Takayuki
Published: September 2020

Background

Paraneoplastic cerebellar degeneration (PCD) is a devastating paraneoplastic syndrome that occasionally occurs in patients with Hodgkin lymphoma (HL). Anti-Ma2 is a well-characterized onconeuronal antibody and one of the causes of PCD. There has been only one previous report of anti-Ma2-associated paraneoplastic syndrome as a complication of HL. Here we present a rare case of anti-Ma2-associated PCD in a patient with nodular lymphocyte-predominant HL (NLPHL).

Case presentation

A 77-year-old man with a 3-month history of gait instability and a 2-month history of oscillopsia was referred to our hospital for further investigation. On examination, his cognition was normal. He had nystagmus in all directions of gaze; specifically, he had horizontal and rotatory nystagmus in the primary position, downbeat nystagmus after right, left, and up gaze, and upbeat nystagmus after down gaze. Although his limb ataxia was mild, his trunk ataxia was so pronounced that he was unable to walk without support. We strongly suspected paraneoplastic syndrome and tested for neuronal autoantibodies. The anti-Ma2 antibody was strongly positive in the blood and cerebrospinal fluid but other antineuronal autoantibodies were negative. Computed tomography showed an enlarged lymph node in the right axilla but no masses. Biopsy confirmed a diagnosis of NLPHL. The NLPHL cells stained with anti-Ma-2 antibody in the cytoplasm, suggesting these abnormal cells contained protein that was cross-reactive with Ma-2.

Conclusions

To the best of our knowledge, this is the first case of anti-Ma2-associated PCD in a patient with NLPHL that was confirmed using immunostaining of the lymph node tissue with anti-Ma2 antibody. Our case confirms an association between anti-Ma2-associated PCD and NLPHL.
Electronic cigarettes may not be a “safer alternative” of conventional cigarettes during pregnancy: evidence from the nationally representative PRAMS data
Authors: Kim Sooyong , Oancea Sanda Cristina
Published: September 2020

Background

Conventional cigarette (CC) smoking is one of the most preventable causes of adverse birth outcomes. Although electronic cigarettes (ECs) are considered to be safer than CCs during pregnancy, the evidence is yet to be presented. This study examines the effects of prenatal EC use on neonatal birth outcomes compared to those of CC smokers and complete tobacco abstainers.

Methods

Data was extracted from 55,251 pregnant women who participated in the Phase 8 survey of the Pregnancy Risk Assessment Monitoring System between 2016 and 2018. Participants were classified into three groups based on their smoking behaviors in the third trimester: complete tobacco abstinence, exclusive CC smoking, or exclusive EC use. Adverse outcomes included infants being small-for-gestational-age (SGA), having low birthweight (LBW), and being born at preterm. EC users were matched to complete abstainers and CC smokers who share the same baseline characteristics in race/ethnicity, age, educational attainment, income, prenatal care adequacy, and first- and second-trimester CC smoking statuses. The association between EC use and adverse birth outcomes were examined by survey-weighted logistic regression analyses in the matched population.

Results

Among participants, 1.0% of women reported having used ECs during the third trimester, 60% of which reported using ECs exclusively. Neonates of EC users were significantly more likely to be SGA (OR 1.76; 95% CI 1.04, 2.96), have LBW (OR 1.53; 95% CI 1.06, 2.22), or be born preterm (OR 1.86; 95% CI 1.11, 3.12) compared to tobacco abstainers. However, odds of EC users’ pregnancies resulting in SGA (OR 0.67; 95% CI 0.30, 1.47), LBW (OR 0.71; 95% CI 0.37, 1.37), or preterm birth (OR 1.06; 95% CI 0.46, 2.48) were not significantly lower than those of CC smokers.

Conclusions

Even after accounting for shared risk factors between prenatal tobacco use and adverse birth outcomes, EC use remains an independent risk factor for neonatal complications and is not a safer alternative to CC smoking during pregnancy. Until further research is completed, all pregnant women are encouraged to abstain from all tobacco products including ECs.
Adding exogenous biglycan or decorin improves tendon formation for equine peritenon and tendon proper cells in vitro
Authors: Pechanec Monica Y. , Boyd Tannah N. , Baar Keith , Mienaltowski Michael J.
Published: September 2020

Background

Tendon injuries amount to one of the leading causes of career-ending injuries in horses due to the inability for tendon to completely repair and the high reinjury potential. As a result, novel therapeutics are necessary to improve repair with the goal of decreasing leg lameness and potential reinjury. Small leucine-rich repeat proteoglycans (SLRPs), a class of regulatory molecules responsible for collagen organization and maturation, may be one such therapeutic to improve tendon repair. Before SLRP supplementation can occur in vivo, proper evaluation of the effect of these molecules in vitro needs to be assessed. The objective of this study was to evaluate the effectiveness of purified bovine biglycan or decorin on tendon proper and peritenon cell populations in three-dimensional tendon constructs.

Methods

Equine tendon proper or peritenon cell seeded fibrin three-dimensional constructs were supplemented with biglycan or decorin at two concentrations (5 nM or 25 nM). The functionality and ultrastructural morphology of the constructs were assessed using biomechanics, collagen content analysis, transmission electron microscopy (TEM), and gene expression by real time – quantitative polymerase chain reaction (RT-qPCR).

Results

SLRP supplementation affected both tendon proper and peritenon cells-seeded constructs. With additional SLRPs, material and tensile properties of constructs strengthened, though ultrastructural analyses indicated production of similar-sized or smaller fibrils. Overall expression of tendon markers was bolstered more in peritenon cells supplemented with either SLRP, while supplementation of SLRPs to TP cell-derived constructs demonstrated fewer changes in tendon and extracellular matrix markers. Moreover, relative to non-supplemented tendon proper cell-seeded constructs, SLRP supplementation of the peritenon cells showed increases in mechanical strength, material properties, and collagen content.

Conclusions

The SLRP-supplemented peritenon cells produced constructs with greater mechanical and material properties than tendon proper seeded constructs, as well as increased expression of matrix assembly molecules. These findings provide evidence that SLRPs should be further investigated for their potential to improve tendon formation in engineered grafts or post-injury.
Comparison of conventional fenestration discectomy with Transforaminal endoscopic lumbar discectomy for treating lumbar disc herniation:minimum 2-year long-term follow-up in 1100 patients
Authors: Li Quanyi , Zhou Yongchun
Published: September 2020

Purpose

To compare the efficacy of conventional interlaminar fenestration discectomy (IFD) with transforaminal endoscopic lumbar discectomy (TELD) for treating lumbar disc herniation (LDH).

Methods

The clinical data of 1100 patients who had been diagnosed with LDH between January 2012 and December 2017 were retrospectively analysed. IFD was performed on 605 patients in Group A, whereas TELD was performed on 505 patients in Group B. The Oswestry Disability Index, Visual Analogue Scale for pain and modified MacNab criteria were used to evaluate the outcomes. The surgery duration, intraoperative blood loss, postoperative off-bed activity and postoperative length of hospital stay were recorded.

Results

The follow-up period ranged from 24 to 60 months, with an average of 43 months. The excellent and good outcome rates were 93.5% in Group A and 92.6% in Group B. There was no significant difference in efficacy between the groups (P > 0.05). However, Group B had significantly less intraoperative blood loss and shorter bed rest duration and postoperative length of hospital stay than Group A (P < 0.05). There were two cases of postoperative recurrence in Group A and three in Group B.

Conclusions

Although conventional IFD and TELD had similar levels of efficacy in treating LDH, TELD had several advantages. There was less intraoperative bleeding, shorter length of hospital stay and shorter bed rest duration. It can be considered a safe and effective surgical option for treating LDH.
Surgery-associated acquired hemophilia A: a report of 2 cases and review of literature
Authors: Khan Umar Zeb , Yang Xiangwu , Masroor Matiullah , Aziz Abdul , Yi Hui , Liu Hai
Published: September 2020

Background

Acquired Hemophilia A (AHA) is a rare bleeding diathesis in patients with no previous personal or family bleeding history. The diagnosis of this disease often delays due to unfamiliarity of physicians with it, which leads to its high mortality rate.

Case presentation

Two cases (one 12 years old female and another 18 years old male) were admitted for right upper abdominal mass and right upper abdominal pain respectively at different times. Pre-operative diagnosis of both cases was congenital choledochal cyst. They suffered continuous gastrointestinal bleeding (hematemesis and melena) with reduced hemoglobin to 54 g/L and 60 g/L after Roux-en-Y anastomosis respectively. To investigate the exact bleeding site, Digital subtraction angiography (DSA) of case 1 showed contrast overflow at small branch of proper hepatic artery but had unremarkable result for case 2, whereas gastroscopy of both cases showed unremarkable results. Multiple surgeries were also performed for hemostatic purpose but each time no active bleeding site was found. Finally, hematologists consultation was mandated in both cases and they were diagnosed as acquired haemophilia A. However, unfortunately case 1 patient could not survive because of sever hemorrhage and infection while Case 2 of 18 years old male survived after proper haemophilia treatment catalog.

Conclusion

Awareness about surgery associated acquired haemophilia A (SAHA) can facilitate quick diagnosis and lifesaving management because the mortality rate in SAHA is high due to lake of knowledge or late recognition of the disease. Bleeding always occurs at surgical sites and it can occur immediately within few hours after surgery in some cases. Hemorrhage may be severe or even life threatening and it presents a special challenge for diagnosis and treatment in a patient who has just undergone a surgical procedure. The treatment strategies for AHA include resumption of hemostasis with either recombinant porcine factor VIII (rpFVIII) or bypassing agents and immunosuppressive therapy to suppress the production of the factor VIII inhibitor.
Qingchang Huashi granule ameliorates experimental colitis via restoring the dendritic cell-mediated Th17/Treg balance
Authors: Jia Jia , Zheng Kai , Shen Hong , Yu Jiangyi , Zhu Ping , Yan Shihai , Xu Yi , Zhu Lei , Lu Yuelin , Gu Peiqing , Feng Wan
Published: September 2020

Background

The balance between T helper 17 (Th17) cells and regulatory T cells (Tregs) is involved in immunological tolerance. Destruction of immunological tolerance by dendritic cell (DC)-mediated T cells is involved in the pathogenesis of ulcerative colitis (UC). Qingchang Huashi granule (QCHS) has been confirmed in the treatment of UC involved by inhibiting the activation of DCs. The aim of this study was to investigate the mechanism through which QCHS restores the Th17/Treg balance by modulating DCs in the treatment of UC.

Methods

The effects of QCHS on Th17 cells, Tregs and DCs were detected in a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis model. Furthermore, we injected QCHS-treated DCs into colitis model to test whether QCHS modulates the Th17/Treg balance via DCs. Tregs and Th17 cells were analyzed by FACS. IL-10, IL-17, and Foxp3 were measured by ELISA, Western blot and qRT-PCR.

Results

Both QCHS and QCHS-treated DCs improved colonic histopathology, diminished Th17 cell differentiation and inhibited IL-17 production while promoting CD4+CD25+Foxp3+ Treg differentiation and augmenting IL-10 and Foxp3 expression in colitis mice. Additionally, QCHS reduced CD86 and MHC-II expression on DCs, decreased IL-12 production ex vivo and restored the Th17/Treg ratio in the colitis model.

Conclusion

The findings of this study indicate that QCHS ameliorates TNBS-induced colitis by restoring the DC-mediated Th17/Treg balance.
Closing the loop on test results to reduce communication failures: a rapid review of evidence, practice and patient perspectives
Authors: Wright Breanna , Lennox Alyse , Graber Mark L. , Bragge Peter
Published: September 2020

Background

Communication failures involving test results contribute to issues of patient harm and sentinel events. This article aims to synthesise review evidence, practice insights and patient perspectives addressing problems encountered in the communication of diagnostic test results.

Methods

The rapid review identified ten systematic reviews and four narrative reviews. Five practitioner interviews identified insights into interventions and implementation, and a citizen panel with 15 participants explored the patient viewpoint.

Results

The rapid review provided support for the role of technology to ensure effective communication; behavioural interventions such as audit and feedback could be effective in changing clinician behaviour; and point-of-care tests (bedside testing) eliminate the communication breakdown problem altogether. The practice interviews highlighted transparency, and clarifying the lines of responsibility as central to improving test result communication. Enabling better information sharing, implementing adequate planning and utilising technology were also identified in the practice interviews as viable strategies to improve test result communication. The citizen panel highlighted technology as critical to improving communication of test results to both health professionals and patients. Patients also highlighted the importance of having different ways of accessing test results, which is particularly pertinent when ensuring suitability for vulnerable populations.

Conclusions

This paper draws together multiple perspectives on the problem of failures in diagnostic test results communication to inform appropriate interventions. Across the three studies, technology was identified as the most feasible option for closing the loop on test result communication. However, the importance of clear, consistent communication and more streamlined processes were also key elements that emerged.

Review registration

The protocol for the rapid review was registered with PROSPERO CRD42018093316.
ACBE, a new base editor for simultaneous C-to-T and A-to-G substitutions in mammalian systems
Authors: Xie Jingke , Huang Xingyun , Wang Xia , Gou Shixue , Liang Yanhui , Chen Fangbing , Li Nan , Ouyang Zhen , Zhang Quanjun , Ge Weikai , Jin Qin , Shi Hui , Zhuang Zhenpeng , Zhao Xiaozhu , Lian Meng , Wang Jiaowei , Ye Yinghua , Quan Longquan , Wu Han , Wang Kepin , Lai Liangxue
Published: September 2020

Background

Many favorable traits of crops and livestock and human genetic diseases arise from multiple single nucleotide polymorphisms or multiple point mutations with heterogeneous base substitutions at the same locus. Current cytosine or adenine base editors can only accomplish C-to-T (G-to-A) or A-to-G (T-to-C) substitutions in the windows of target genomic sites of organisms; therefore, there is a need to develop base editors that can simultaneously achieve C-to-T and A-to-G substitutions at the targeting site.

Results

In this study, a novel fusion adenine and cytosine base editor (ACBE) was generated by fusing a heterodimer of TadA (ecTadAWT/*) and an activation-induced cytidine deaminase (AID) to the N- and C-terminals of Cas9 nickase (nCas9), respectively. ACBE could simultaneously induce C-to-T and A-to-G base editing at the same target site, which were verified in HEK293-EGFP reporter cell line and 45 endogenous gene loci of HEK293 cells. Moreover, the ACBE could accomplish simultaneous point mutations of C-to-T and A-to-G in primary somatic cells (mouse embryonic fibroblasts and porcine fetal fibroblasts) in an applicable efficiency. Furthermore, the spacer length of sgRNA and the length of linker could influence the dual base editing activity, which provided a direction to optimize the ACBE system.

Conclusion

The newly developed ACBE would expand base editor toolkits and should promote the generation of animals and the gene therapy of genetic diseases with heterogeneous point mutations.
Association between Neu5Gc carbohydrate and serum antibodies against it provides the molecular link to cancer: French NutriNet-Santé study
Authors: Bashir Salam , Fezeu Leopold K. , Leviatan Ben-Arye Shani , Yehuda Sharon , Reuven Eliran Moshe , Szabo de Edelenyi Fabien , Fellah-Hebia Imen , Le Tourneau Thierry , Imbert-Marcille Berthe Marie , Drouet Emmanuel B. , Touvier Mathilde , Roussel Jean-Christian , Yu Hai , Chen Xi , Hercberg Serge , Cozzi Emanuele , Soulillou Jean-Paul , Galan Pilar , Padler-Karavani Vered
Published: September 2020

Background

High consumption of red and processed meat is commonly associated with increased cancer risk, particularly colorectal cancer. Antibodies against the red meat-derived carbohydrate N-glycolylneuraminic acid (Neu5Gc) exacerbate cancer in “human-like” mice. Human anti-Neu5Gc IgG and red meat are both independently proposed to increase cancer risk, yet how diet affects these antibodies is largely unknown.

Methods

We used world global data to demonstrate that colorectal cancer incidence and mortality are associated with increased national meat consumption. In a well-defined large cohort, we used glycomics to measure daily Neu5Gc intake from red meat and dairy, and investigated serum as well as affinity-purified anti-Neu5Gc antibodies. Based on 24-h dietary records, daily Neu5Gc intake was calculated for 19,621 subjects aged ≥ 18 years of the NutriNet-Santé study. Serum and affinity-purified anti-Neu5Gc antibodies were evaluated by ELISA and glycan microarrays in representative 120 individuals, each with at least eighteen 24-h dietary records (aged 45–60, Q1–Q4; aged > 60, Q1 and Q4; 10 men/women per quartile).

Results

We found that high-Neu5Gc diet, gender, and age affect the specificity, levels, and repertoires of anti-Neu5Gc IgG immune responses, but not their affinity. Men consumed more Neu5Gc than women, mostly from red meat (p = 0.0015), and exhibited higher overall serum anti-Neu5Gc IgG levels by ELISA (3.94 ng/μl versus 2.22 ng/μl, respectively; p = 0.039). Detailed glycan microarray analysis against 56 different glycans revealed high Neu5Gc-specificity with increased anti-Neu5Gc IgG and altered repertoires, associated with higher consumption of Neu5Gc from red meat and cow dairy. Affinity purification of serum anti-Neu5Gc antibodies revealed increased levels and biased array repertoire patterns, without an increase in antibody affinity, in individuals consuming higher Neu5Gc levels. Furthermore, in a high-meat diet, antibody diversity patterns on glycan microarrays shifted towards Neu5Gcα3-linked glycans, increasing the α3/α6-glycans ratio score.

Conclusions

We found a clear link between the levels and repertoire of serum anti-Neu5Gc IgG and Neu5Gc intake from red meat and dairy. These precise rational methodologies allowed to develop a Gcemic index to simplify the assessment of Neu5Gc in foods that could potentially be adapted for dietary recommendations to reduce cancer risk.
The pathogenesis of a North American H5N2 clade 2.3.4.4 group A highly pathogenic avian influenza virus in surf scoters (Melanitta perspicillata)
Authors: Luczo Jasmina M. , Prosser Diann J. , Pantin-Jackwood Mary J. , Berlin Alicia M. , Spackman Erica
Published: September 2020

Background

Aquatic waterfowl, particularly those in the order Anseriformes and Charadriiformes, are the ecological reservoir of avian influenza viruses (AIVs). Dabbling ducks play a recognized role in the maintenance and transmission of AIVs. Furthermore, the pathogenesis of highly pathogenic AIV (HPAIV) in dabbling ducks is well characterized. In contrast, the role of diving ducks in HPAIV maintenance and transmission remains unclear. In this study, the pathogenesis of a North American A/Goose/1/Guangdong/96-lineage clade 2.3.4.4 group A H5N2 HPAIV, A/Northern pintail/Washington/40964/2014, in diving sea ducks (surf scoters, Melanitta perspicillata) was characterized.

Results

Intrachoanal inoculation of surf scoters with A/Northern pintail/Washington/40964/2014 (H5N2) HPAIV induced mild transient clinical disease whilst concomitantly shedding high virus titers for up to 10 days post-inoculation (dpi), particularly from the oropharyngeal route. Virus shedding, albeit at low levels, continued to be detected up to 14 dpi. Two aged ducks that succumbed to HPAIV infection had pathological evidence for co-infection with duck enteritis virus, which was confirmed by molecular approaches. Abundant HPAIV antigen was observed in visceral and central nervous system organs and was associated with histopathological lesions.

Conclusions

Collectively, surf scoters, are susceptible to HPAIV infection and excrete high titers of HPAIV from the respiratory and cloacal tracts whilst being asymptomatic. The susceptibility of diving sea ducks to H5 HPAIV highlights the need for additional research and surveillance to further understand the contribution of diving ducks to HPAIV ecology.
Sex and gender analysis in knowledge translation interventions: challenges and solutions
Authors: Gogovor Amédé , Mollayeva Tatyana , Etherington Cole , Colantonio Angela , Légaré France ,   on behalf of the GIKT Group, Adisso Lionel , Boet Sylvain , Brabete Andreea , Colantonio Angela , Etherington Cole , Gogovor Amédé , Greaves Lorraine , Laberge Marie , Légaré France , Messing Karen , Mollayeva Tatyana , Rhugenda Sylvie-Marianne , Sibley Kathryn , Siebert Cora , Straus Sharon , Tanguay Dominique , Tannenbaum Cara , Vaillancourt Cathy , van Hoof Krystle
Published: September 2020

Sex and gender considerations are understood as essential components of knowledge translation in the design, implementation and reporting of interventions. Integrating sex and gender ensures more relevant evidence for translating into the real world. Canada offers specific funding opportunities for knowledge translation projects that integrate sex and gender. This Commentary reflects on the challenges and solutions for integrating sex and gender encountered in six funded knowledge translation projects. In 2018, six research teams funded by the Canadian Institutes of Health Research’s Institute of Gender and Health met in Ottawa to discuss these challenges and solutions. Eighteen participants, including researchers, healthcare professionals, trainees and members of the Institute of Gender and Health, were divided into two groups. Two authors conducted qualitative coding and thematic analysis of the material discussed. Six themes emerged, namely Consensus building, Guidance, Design and outcomes effectiveness, Searches and recruitment, Data access and collection, and Intersection with other determinants of health. Solutions included educating stakeholders on the use of sex and gender concepts, triangulating perspectives of researchers and end-users, and participating in organisations and committees to influence policies and practices. Unresolved challenges included difficulty integrating sex and gender considerations with principles of patient-oriented research, a lack of validated measurement tools for gender, and a paucity of experts in intersectionality. We discuss our findings in the light of observations of similar initiatives elsewhere to inform the further progress of integrating sex and gender into the knowledge translation of health services research findings.
Lentiviral delivery of combinatorial CAR/CRISPRi circuit into human primary T cells is enhanced by TBK1/IKKɛ complex inhibitor BX795
Authors: Li Lingyu , Gao Yuan , Srivastava Richa , Wang Wei , Xiong Qinghui , Fang Zhiming , Pelayo Alejandra , Denson Carolyn , Goswami Angshumala , Harari-Steinfeld Rona , Yang Zhifen , Weng Lihong , Qi Lei Stanley , Marincola Francesco M.
Published: September 2020

Background

Adoptive transfer of engineered immune cells is a promising strategy for cancer treatment. However, low transduction efficiency particularly when large payload lentiviral vectors are used on primary T cells is a limitation for the development of cell therapy platforms that include multiple constructs bearing long DNA sequences. RB-340-1 is a new CAR T cell that combines two strategies in one product through a CRISPR interference (CRISPRi) circuit. Because multiple regulatory components are included in the circuit, RB-340-1 production needs delivery of two lentiviral vectors into human primary T cells, both containing long DNA sequences. To improve lentiviral transduction efficiency, we looked for inhibitors of receptors involved in antiviral response. BX795 is a pharmacological inhibitor of the TBK1/IKKɛ complex, which has been reported to augment lentiviral transduction of human NK cells and some cell lines, but it has not been tested with human primary T cells. The purpose of this study was to test if BX795 treatment promotes large payload RB-340-1 lentiviral transduction of human primary T cells.

Methods

To make the detection of gene delivery more convenient, we constructed another set of RB-340-1 constructs containing fluorescent labels named RB-340-1F. We incorporated BX795 treatment into the human primary T cell transduction procedure that was optimized for RB-340-1F. We tested BX795 with T cells collected from multiple donors, and detected the effect of BX795 on T cell transduction, phenotype, cell growth and cell function.

Results

We found that BX795 promotes RB-340-1F lentiviral transduction of human primary T cells, without dramatic change in cell growth and T cell functions. Meanwhile, BX795 treatment increased CD8+ T cell ratios in transduced T cells.

Conclusions

These results indicate that BX795 treatment is effective, and might be a safe approach to promote RB-340-1F lentiviral transduction of human primary T cells. This approach might also be helpful for other T cell therapy products that need delivery of complicated platform via large payload lentiviral vectors.
Splenic sympathetic signaling contributes to acute neutrophil infiltration of the injured spinal cord
Authors: Monteiro Susana , Pinho Andreia G. , Macieira Mara , Serre-Miranda Cláudia , Cibrão Jorge R. , Lima Rui , Soares-Cunha Carina , Vasconcelos Natália L. , Lentilhas-Graça José , Duarte-Silva Sara , Miranda Alice , Correia-Neves Margarida , Salgado António J. , Silva Nuno A.
Published: September 2020

Background

Alterations in the immune system are a complication of spinal cord injury (SCI) and have been linked to an excessive sympathetic outflow to lymphoid organs. Still unknown is whether these peripheral immune changes also contribute for the deleterious inflammatory response mounted at the injured spinal cord.

Methods

We analyzed different molecular outputs of the splenic sympathetic signaling for the first 24 h after a thoracic compression SCI. We also analyzed the effect of ablating the splenic sympathetic signaling to the innate immune and inflammatory response at the spleen and spinal cord 24 h after injury.

Results

We found that norepinephrine (NE) levels were already raised at this time-point. Low doses of NE stimulation of splenocytes in vitro mainly affected the neutrophils’ population promoting an increase in both frequency and numbers. Interestingly, the interruption of the sympathetic communication to the spleen, by ablating the splenic nerve, resulted in reduced frequencies and numbers of neutrophils both at the spleen and spinal cord 1 day post-injury.

Conclusion

Collectively, our data demonstrates that the splenic sympathetic signaling is involved in the infiltration of neutrophils after spinal cord injury. Our findings give new mechanistic insights into the dysfunctional regulation of the inflammatory response mounted at the injured spinal cord.
Neurocognitive impairment and evidence-based treatment options in Bipolar disorder
Authors: Fountoulakis Konstantinos N.
Published: September 2020

Background

The current paper briefly summarizes the literature on the neurocognitive deficit and its treatment in BD patients.

Methods

The material was chosen on the basis of previous systematic reviews the author has taken part in.

Results

The data so far suggest that the deficit is qualitatively similar but quantitatively milder in comparison to schizophrenia, it is present already since the first episode, is weakly related to mood symptoms and somewhat stronger to psychotic symptoms, it probably determines much of the disability and treatment is problematic. This deficit is also present during periods of euthymia. The possible adverse effect of psychotropic medication is rather small if any at all and is confounded by the specific clinical symptoms, for which medication is used for their treatment. This is especially true concerning antipsychotics and psychotic symptoms. The origin and the etiopathogenesis of the core neurocognitive impairment remain elusive. The presence of a neurodegenerative and of a neurodevelopmental component has both data in favor and against and they are both the focus of debate.

Conclusions

Treatment of the neurocognitive deficit and restoration of functioning is problematic. The data are limited and treatment options are few and with a weak overall effect. Pharmacological treatments, ECT and rTMS present some hard data, while the literature is inconclusive concerning psychotherapeutic interventions.
Physical rehabilitation in Iran after international sanctions: explored findings from a qualitative study
Authors: Shahabi Saeed , Teymourlouy Ahmad Ahmadi , Shabaninejad Hosein , Kamali Mohammad , Lankarani Kamran Bagheri , Mojgani Parviz
Published: September 2020

Background

Although the main aims of sanctions are the political and economic pressures on governments, literature has demonstrated the harsh effects of sanctions on the general public, especially on the patients, poor and disabled people. Since the international sanctions regime negatively affected almost all dimensions of Iran’s health sector, this qualitative study was conducted to investigate the situation of the physical rehabilitation sector after these sanctions.

Methods

This qualitative study was conducted from January 2019 to June 2019 in Iran using Skype, telephone, and face-to-face in-depth semi-structured interviews. Purposive and snowball sampling approaches were used to identify the participants. Also, framework analysis approach was applied to analyze the collected data.

Results

In total, 38 individuals including health policy-maker, faculty member, rehabilitation expert, Physiotherapist, Occupational therapist, and Orthotist/Prosthetist, were involved in the study. Based on our findings, a number of challenges facing the Iranian physical rehabilitation sector during the international sanctions period included: 1) socioeconomic challenges (inadequate funding, rising inflation rate, high unemployment rate, catastrophic expenditures, and inappropriate employment status of practitioners); 2) education challenges (decreased international collaboration and shortage of training devices and materials); 3) international challenges (rising issues in accessing services for patients from neighborhood countries); and 4) service delivery challenges (shortage of raw materials for producing the orthoses and prostheses, hardening of the importing the needed equipment, inappropriate infrastructures, and impossibility to use external assistance).

Conclusion

After international sanctions, the Iranian physical rehabilitation sector has faced considerable multifaceted challenges. Therefore, the international community must be aware of the situation and be concerned about the irreparable consequences.