bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and characterization of Chitosan-Catechol conjugates: Development and in vitro, in silico and in vivo evaluation of mucoadhesive pellets of lafutidine
Authors: Kaur Loveleen , Thakur Ajay Kumar , Kumar Pradeep , Singh Inderbir
Published: March 2021

Present study was aimed to synthesize and characterize Chitosan-Catechol conjugates and to design and develop mucoadhesive pellets loaded with lafutidine. SEM images indicated the presence of fibrous structures responsible for enhanced mucoadhesive potential of Chitosan-Catechol conjugates. Thermodynamic stability and amorphous nature of conjugates was confirmed by DSC and XRD studies respectively. Rheological studies were used to evaluate polymer mucin interactions wherein strong interactions between Chitosan-Catechol conjugate and mucin was observed in comparison to pristine chitosan and mucin. The mucoadhesion potential of Chitosan-Catechol (Cht-C) versus Chitosan (Cht) was assessed in silico using molecular mechanics simulations and the results obtained were compared with the in vitro and ex vivo results. Cht-C/mucin demonstrated much higher energy stabilization (∆E ≈ −65 kcal/mol) as compared to Cht/mucin molecular complex. Lafutidine-loaded pellets were prepared from Chitosan (LPC) and Chitosan-Catechol conjugates (LPCC) and were evaluated for various physical properties viz. flow, circularity, roundness, friability, drug content, particle size and percent mucoadhesion. In vitro drug release studies on LPC and LPCC pellets were performed for computing t50%, t90% and mean dissolution time. The values of release exponent from Korsmeyer-Peppas model was reported to be 0.443 and 0.759 for LPC and LPCC pellets suggesting Fickian and non-Fickian mechanism representing drug release, respectively. In vivo results depicted significant controlled release and enhanced residence of the drug after being released from the chitosan-catechol coated pellets. Chitosan-Catechol conjugates were found to be a promising biooadhesive polymer for the development of various mucoadhesive formulations.
Experimental study on repair of large segmental bone defects of goat femur by nano calcium-deficient hydroxyapatite-multi (amino acid) copolymer membrane tubes
Authors: Xiong Yan , Duan Hong , Zhang Bin , Ren Cheng , Yu Zeping , Yan Yonggang
Published: March 2021

Objective

The purpose of this study was to observe feasibility of nano calcium-deficient hydroxyapatite-multi (amino acid) copolymer (n-CDHA-MAC) membrane tubes in repairing goat femurs’ large defects.

Methods

Twelve goats were divided into two groups, whose femurs were created 30 mm segmental bone defects and then implants were performed. In experimental group, the bone defect of right femur was reconstructed by n-CDHA-MAC membrane tube, while left side was reconstructed by allogenic bone tube in control group. Every three goats were sacrificed at 4, 8, 16, 24 weeks after operation respectively. General observation, X-ray analysis, histology, Scanning electron microscope (SEM) examination and protein level comparison of BMP-2 were conducted to evaluate the effects of repairing segmental bone defects.

Results

All goats recovered well from anesthesia and surgical interventions. The radiographic evaluations showed that periosteal reaction outside of the membrane tubes and allogenic bone tubes were observed 4 weeks after surgery. At 16 weeks, callus was continuously increased in experimental group, which was more obvious than control group. At 24 weeks, callus outside of the membrane tubes connected together. Histologic evaluation showed fibro-cartilage callus was evolved into bony callus in experimental group, which was more obvious than control group at 8 and 16 weeks. The protein expression level of BMP-2 increased at 4, 8 weeks and peaked at 16 weeks in experimental groups. There were statistical differences at 8 and 16 weeks ( P < 0.05). At each time point in 8, 16, 24 weeks after surgery, the bending stiffness, torsional stiffness and compressive strength of the two groups were similar, and there was no significant difference ( P > 0.05).

Conclusions

This novel surface degradation n-CDHA-MAC membrane tube has good ability to maintain enough membrane space, which can provide long-term and stable biomechanical support for large bone defects and integrate well with the surrounding bone.
Individual- and School-level Predictors of Latent Profiles of Bullying Victimization: Comparing South Korea and the United States
Authors: Han Yoonsun , Lee Shinhye , Cho Eunah , Song Juyoung , Hong Jun Sung
Published: March 2021

This cross-national research investigated nationally representative adolescents from South Korea and the United States, explored similarities and differences in latent profiles of bullying victimization between countries, and examined individual- and school-level variables that predict such latent profiles supported by the Social Disorganization Theory. The fourth-grade sample of the 2015 Trends in International Mathematics and Science Study from South Korea ( N = 4,669) and the United States ( N = 10,029) was used to conduct a latent profile analysis based on eight items of the bullying victimization questionnaire. Multilevel logistic regression was conducted using latent profiles as dependent variables. Independent variables include individual-level (material goods, school absence, academic interest, school belonging) and school-level (concentration of affluent families, school resources, the severity of delinquency, academic commitment) factors. More similarities existed than differences in the latent groups of bullying victimization between South Korea ( rare, low-moderate, verbal-relational-physical, and multi-risk) and the United States ( rare, low-moderate, verbal-relational, and multi-risk). Evidence for school-level variables as predictors of bullying victimization profiles was stronger for adolescents in the United States, with a concentration of affluent families and severity of delinquency being significant in four of the six models. For the South Korean sample, the severity of delinquency predicted bullying victimization in only one model. Examination of both individual- and school-level factors that predict unique bullying victimization experiences grounded in Social Disorganization Theory may be informative for addressing key areas of intervention—especially at the school-level context in which victimization primarily takes place and where anti-bullying intervention programs are often provided.
Human impact and landscape changes between 3000 and 1000 BC on the Tropea Promontory (Calabria, Italy)
Authors: Di Lorenzo Halinka , Jung Reinhard , Pacciarelli Marco , Weninger Bernhard , Russo Ermolli Elda
Published: March 2021

Pollen data were collected from a one-meter peat succession recovered from the top of the Tropea Promontory (Calabria), a territory continuously inhabited throughout Prehistory and Protohistory. The peat was deposited in a small pond/marsh that was gradually filled up. Six 14C dates allowed the peat growth to be constrained to between ca. 3000 and 1000 calBC. Considerable landscape and land use changes occurred in the area in that time interval, due to both environmental changes and intensive human activities. An open landscape with scattered oak woods characterized the high plain, whereas on the wet soils surrounding the marsh, wet woodlands ( Alnus), and hygrophilous vegetation (Cyperaceae) developed, their relative abundance being used to mark the local environmental evolution. The occurrence of different anthropogenic indicators reveals that the area was exploited for agricultural practices (cereal cultivation) and livestock grazing, the latter being the main activity practiced around the marsh between the Eneolithic (stable settlements) and the Early-Middle Bronze Age (seasonal presence). The possibility of climatic influence on the peat evolution was studied by comparisons with well-dated isotope records. The marsh contraction phase roughly coincides with the 4.2 ka calBP event, while the end of peat accumulation postdates the 3.0 ka calBP rapid climate change event.
Health Hazards for Women in Tobacco Cultivation in Andhra Pradesh, India
Authors: Kumar Chikkala Kranthi
Published: March 2021

Women workers in Andhra Pradesh play a crucial role in tobacco cultivation. This article discusses their involvement in regular operations and examines and assesses the health hazards they risk in the course of their work. There is an uneconomical use of human energy due to long hours of work, task postures deleterious to the body and exposure to pesticides. The tedious work, inhospitable environment and poor socio-economic conditions lead to chronic morbidity. It is unfortunate that these workers are not getting the protection of laws that apply to them. Massive intervention in this sector is a responsibility of the departments of labour and public health.
Land Loss with Compensation: What Are the Determinants of Income Among Households in Central Vietnam?
Authors: Phuc Nguyen Quang , van Westen A. C. M. (Guus) , Zoomers Annelies
Published: March 2021

The purpose of this study is to investigate the determinants of household income following the loss of land owing to urban expansion in central Vietnam. Using data mainly from household surveys in the peri-urban areas of Hue city, the regression model indicates that demographic factors and livelihood strategy choices have important impacts on household income; financial compensation and support packages do not appear to be strong determinants of household income after the loss of land. This implies a failure of the current compensation programmes in the process of compulsory land acquisition, because the government believes that compensation packages make important contributions to livelihood reconstruction. This study suggests that investing in education and skill training for household members affected by land loss as well as assistance in converting compensation money into an adequate livelihood should be taken into consideration.
Role of Small and Medium Enterprise Clusters in Urban–Rural Linkage: A Study Based on Manufacturing SMEs of Khulna City, Bangladesh
Authors: Ranman S. M. Towhidur , Kabir Md Ahsanul
Published: March 2021

This study explores the role of small and medium enterprise (SME) clusters in urban–rural linkages, an increasingly acceptable strategy in policy planning for regional development. As this approach to development has mostly been studied from a macro perspective, there is paucity of research from a micro perspective, particularly in the context of Bangladesh. This study, thus, aims to explore the contribution of manufacturing SME industry clusters in linking urban and rural regions. The data used in the study has been collected from 119 SME entrepreneurs using a structured questionnaire. Factor analysis and logistic regression have been applied to explore the contribution of industrial clusters in urban–rural linkages, focusing on the city of Khulna as the study area. The findings show that such SME clusters can positively contribute towards linking the two territories through two main forces, namely, funds and mobility. The findings provide useful insights for policymakers and urban planners to take initiatives for identifying and developing such SME industry clusters instead of focusing on the development of large industries, both in urban and rural areas to enhance balanced regional development. In highlighting the contribution of SME industry cluster as a micro level actor in the process of urban-rural integration, the study aims to make a meaningful contribution to literature in the field of development planning.
Particle entrapment in elliptical, elastohydrodynamic, rough contacts and the influence of intermolecular (van der Waals) forces
Authors: Nikas George K
Published: March 2021

The entrapment/rejection process of spherical, rigid microparticles in elliptical, rough elastohydrodynamic contacts is modelled. An earlier model of the author is extended to include van der Waals intermolecular forces, in addition to mechanical (reaction and friction) and fluid–particle forces. Surface roughness effects are also introduced in terms of the intermolecular force formulation and in the microscale friction (particle–asperity) sub-model. Possibilities related to particle entry into a contact are quantified by weight factors and performance indices. A total entrapment index is defined and linked to the probability of particle entrapment. A parametric analysis investigates the effect of the intermolecular particle force on the entrapment probability by varying the contact load, lubricant viscosity, elastic modulus of the contacting solids, contact velocity and the macroscopic (Coulomb) coefficient of friction.
Will rivals enter or wait outside when faced with litigation risk? Patent litigation in complex product industries and international market entry
Authors: Onoz Ergun , Giachetti Claudio
Published: March 2021

A spiral of patent infringement litigation among rival firms is a phenomenon often observed in complex product industries, where products comprise numerous separately patentable elements. Theoretically grounded in the awareness–motivation–capability framework of competitive dynamics, this article contributes to the literature on patent strategy and international market entry by looking at how, in a complex product industry, the intensity of patent litigation in a country affects a firm’s decision to enter that country. Our results show that the intensity of patent litigation in a country is a deterrent for potential entrants and has a negative effect on a firm’s likelihood of entering that country. We also show that a firm’s previous experience with patent litigation ( awareness component), the share of a firm’s current patent applications in a target country ( motivation component), and the size of a firm’s patent stock ( capability component) moderate the relationship between a country’s patent litigation intensity and a firm’s likelihood of entering that country. We thus shed light on the joint effect of macro- and micro-level patent-related variables on a firm’s market entry decisions. We test our hypotheses with a comprehensive panel of patenting and entry strategies of 84 mobile phone vendors and their patent litigation battles in 45 countries, from 2003 to 2015.
High velocity impact properties of composites reinforced by stitched and unstitched glass woven fabrics
Authors: Behroozi Zeynab , Nosraty Hooshang , Tehrani Majid
Published: March 2021

The present research aimed to investigate the effect of stitching angle and stacking sequence of stitched layers on high velocity impact behavior of composites reinforced by glass woven fabrics. To study the effect of stitching angle on ballistic impact behavior, six different angles of (0°), (90°), (45°), (0°,90°), (±45°) and (0°,90°,±45°) were chosen as stitching angles. These stitching angles were applied on eight layers of glass woven fabric. To study the effect of stacking sequence of stitched layers, a different number of layers were stitched together with the angle of 0°. Unstitched and stitched composites were exposed to high velocity impact with 180 m/s using a spherical projectile. The residual velocity of projectile and dimensions of damage area on the composites’ front and back sides were measured. It was found that the sample with the 45° stitching angle had the best behavior against ballistic impact and its energy absorption was significantly higher than the other samples. Stitching also reduces damage area in front and back sides of the composites and inhibits delamination.
The elusive Malayan tiger ‘captured’: A systematic review of research on educational leadership and management in Malaysia
Authors: Adams Donnie , Thien Lei Mee , Chuin Elly Chin Yen , Semaadderi Pavithra
Published: March 2021

Substantial progress has been made in the knowledge base of educational leadership and management (EDLM) in societies across the world. However, the evidence base in developing countries such as Malaysia remains limited. Thus, this article reports the results of a systematic review of research on EDLM in Malaysia. The review aimed at describing key features of the Malaysian knowledge base in EDLM with respect to publication volume, journal outlets, types of papers published, distribution of knowledge production across its states and key scholars, and the composition of research topics, methods, and maturity of its knowledge production. The review database encompassed 328 journal articles in English and Malay language published on EDLM in Malaysia. Systematic methods were applied in the identification of sources and data extraction from the journal articles. Data analysis relied primarily on quantitative methods for data interpretation to reveal the variability in patterns of knowledge production in Malaysia EDLM. The review found that the Malaysian literature in EDLM is largely contemporary; however, it is an ‘immature but emerging literature’ which bears similarities to literatures in other developing societies in Asia. Recommendations are made for topics, methods and other areas where capacity development is warranted.
Platelet disorders
Authors: Forrest Dominique Jade
Published: March 2021

Platelets play a vital role in haemostasis; therefore, an increase or decrease in levels or a disorder of platelet function can lead to symptoms such as easy bruising and excessive bleeding, particularly from mucocutaneous sites. Patients may also report symptoms associated with the underlying condition. Platelet disorders pose a particular challenge for primary care, due to the vast array of potential causes and clinical outcomes, ranging from little effect to life-threatening problems. Initial assessment in primary care should aim to identify those requiring urgent investigation or treatment, while also determining an underlying cause and potential complications.
Fear Avoidance After Injury and Readiness to Return to Sport in Collegiate Male and Female Gaelic Games Players
Authors: O’Connor Siobhán , Moran Kieran , Sheridan Aishling , Brady Shaunagh , Bruce Conor , Beidler Erica , O’Hagan Anna Donnla , Whyte Enda
Published: March 2021

Background:

Injuries are common in collegiate Gaelic games, and negative psychological responses to injury, such as fear avoidance and a lack of psychological readiness to return to sport, can affect players during their rehabilitation and their subsequent return to sport. Thus, identifying these responses in players can allow clinicians to address these issues during rehabilitation. This study aimed to examine fear avoidance and psychological readiness to return to sport in collegiate Gaelic games players.

Hypothesis:

Collegiate Gaelic games players will experience similar levels of fear avoidance and psychological readiness to return to sport as other adult athletes.

Study Design:

Cohort study.

Level of Evidence:

Level 3.

Methods:

Male (n = 150) and female (n = 76) players from 1 Irish collegiate institution were recruited. Players that were injured over 1 collegiate season completed the Athlete Fear Avoidance Questionnaire (AFAQ) immediately after the injury and the Injury-Psychological Readiness to Return to Sport (I-PRRS) Scale once cleared to return to sport. An injury report form was also completed. The overall AFAQ (sum of 10 items) and I-PRRS (sum of 6 items/10) scores were calculated.

Results:

Seventy-three injuries (n = 73) occurred, and injured players had a mean overall AFAQ and I-PRRS score of 22.6 ± 5.3 and 46.4 ± 8.8, respectively. Just less than half (47.9%) of players were deemed psychologically unready to return to sport when cleared physically. After severe injuries, significantly higher overall AFAQ scores than mild injuries ( P = 0.01) and lower overall I-PRRS than moderate injuries ( P < 0.0001) was noted. For the overall scores, no gender differences were observed.

Conclusion:

Fear avoidance and lowered confidence levels before return to sport occurs in collegiate Gaelic games players similar to other student-athletes.

Clinical Relevance:

Identification of fear avoidance or low readiness to return to sport, particularly after serious injury, is important to implement psychosocial support during their rehabilitation.
Experiences of patients with pelvic radiation injuries after cancer treatment undergoing hyperbaric oxygen therapy: A phenomenological-hermeneutical study
Authors: Velure Grete K. , Müller Bernd , Aa. Hauken May
Published: March 2021

Radiotherapy of pelvic cancers may cause severe tissue injuries, and hyperbaric oxygen therapy (HBOT) is one of few treatment alternatives. As part of a longitudinal, mixed-methods study, this study’s aim was to explore pelvic cancer survivors’ experiences of undergoing such treatment. Using a phenomenological-hermeneutical design, in-depth interviews of 20 cancer survivors were conducted and analysed using systematic text condensation. This study is reported in accordance with COREQ. The informants’ experiences were identified as: Approaching an unknown world, From feeling worried to becoming familiar, A long-lasting treatment course, and The treatment course went better than expected. Despite information prior to the treatment, informants were worried about HBOT but were still motivated to try it. A combination of relevant information, clear routines, person-centred care, peer support, and limited side effects seem to be important factors for patients’ experiences of safety from this treatment.
Geometric Analysis of the Bilobed Flap for Nasal Reconstruction Surgery
Authors: Henick Daniel , Ampem-Darko Kelvin K. , Sayegh Farah , Sanati-Mezrahi Paymon , Bhatt Mehul , Taub Peter J.
Published: March 2021

Background: Reconstruction of the nose can be difficult due to its complex anatomical features. In 1989, Zitelli described a modified version of the bilobed flap design technique using 45° and 90° angles to improve nasal reconstructions. While the bilobed flap is still frequently referenced in scholarly literature, there seems to be inconsistency in preoperative flap design; these deviations can lead to suboptimal outcomes. The authors aim to illustrate the variability in bilobed flap execution and provide guidelines in preoperative design to improve consistency. Methods: A geometrically-based approach was used to characterize the inconsistency of bilobed repair technique. The pre-operative design images from fifteen scholarly articles were analyzed via a series of measurements and computations to quantify the angle of rotation and dimensions for the primary and secondary lobes. The “Error Quotient” was a calculated ratio that objectively measured the extent to which a bilobed design deviated from Zitelli’s specifications. Results: There was a noticeable variability in the design of both the primary and secondary lobes. Bilobed designs with smaller angles of rotation, particularly of the first lobe, were associated with higher Error Quotients and greater amounts of deviation from Zitelli’s design. Designs with the smallest Error Quotients had a primary lobe rotation that approached 45°. Conclusion: Consistency of application of the bilobed flap should be established to allow for optimal results, particularly with emphasis on design of the primary lobe. This can be accomplished by including a disposable protractor and marker in their sterile kit to measure a 45° rotation.
Mineralogy and chemistry of a new halloysite deposit from the Rio de Janeiro pegmatite province, south-eastern Brazil
Authors: Salgado-Campos Victor Matheus Joaquim , Bertolino Luiz Carlos , da Silva Francisco José , Mendes Julio Cezar , Neumann Reiner
Published: March 2021

Halloysite is a 1:1 dioctahedral clay mineral that has been studied widely for applications in nanotechnology and as a mineral exploration guide for recognizing regolith-hosted heavy rare earth element (HREE) deposits. In Brazil, pegmatites from the state of Rio de Janeiro have been catalogued, but their potential to host halloysite deposits has never been studied. After a mineral exploration programme, one pegmatite with considerable halloysite contents and economic potential was discovered. This study reports the mineralogical and chemical characterization of the halloysite of this pegmatite and evaluates the possibility of clay-adsorbedHREEdeposits, like that in the Zudong (China) regolith-hostedHREEdeposit. Seven samples were collected in horizontal channels. Bulk samples and clay fractions (<2 μm) were analysed by quantitative mineral analysis (X-ray diffraction/Rietveld method), chemical analysis (major elements by X-ray fluorescence and Y, U, Th and rare earth elements by inductively coupled plasma mass spectrometry), scanning electron microscopy, Fourier-transform infrared spectroscopy, particle-size analysis, nitrogen physisorption and cation-exchange capacity. Mixed polygonal/cylindrical halloysite-7Å in concentrations between 6.3 and 35.4 wt.% in bulk samples and between 58.0 and 89.8 wt.% in the clay fractions were identified in the pegmatite. The clay fractions presented an average chemical composition of 45.46 wt.% SiO2, 36.10 wt.% Al2O3, 14.62 wt.% loss on ignition and 1.04 wt.% Fe2O3, as well as technological properties close to those observed in world-class halloysite deposits such as Dragon Mine (USA) and Matauri Bay (New Zealand). The clay minerals did not present significantHREEcontents.
Brentuximab vedotin in combination with chemotherapy for pediatric patients with ALK+ ALCL: results of COG trial ANHL12P1
Authors: Lowe Eric J. , Reilly Anne F. , Lim Megan S. , Gross Thomas G. , Saguilig Lauren , Barkauskas Donald A. , Wu Rui , Alexander Sarah , Bollard Catherine M.
Published: March 2021

Approximately 30% of pediatric patients with anaplastic large cell lymphoma (ALCL) relapse. Although brentuximab vedotin has demonstrated excellent activity in ALCL, it has not been used for newly diagnosed patients. Children’s Oncology Group (COG) trial ANHL12P1 determined the toxicity and efficacy of brentuximab vedotin with chemotherapy in children with newly diagnosed nonlocalized anaplastic large cell lymphoma kinase (ALK)+/CD30+ ALCL. From 2013 to 2017, 68 children with ALK+ ALCL were enrolled and received brentuximab vedotin. All patients received 5-day prophase, followed by 6 cycles of chemotherapy. Brentuximab vedotin was given on day 1 of each of the 6 cycles. Of the 67 patients eligible for toxicity evaluation, 66 completed all 6 cycles of chemotherapy, resulting in 399 evaluable cycles. There were no toxic deaths, no case of progressive multifocal leukoencephalopathy syndrome, and no case of grade 3 or 4 neuropathy. The 2-year event-free survival (EFS) was 79.1% (95% confidence interval [CI], 67.2-87.1). The 2-year overall survival (OS) was 97.0% (95% CI, 88.1-99.2). Fourteen patients relapsed. Eleven of 14 (79%) relapses occurred within 10 months of diagnosis; only 1 patient (1.5%) relapsed during therapy. Quantitative reverse transcription polymerase chain reaction for NPM-ALK at baseline (minimal disseminated disease) demonstrated prognostic value for EFS (P = .0004). Overall, the addition of brentuximab vedotin to standard chemotherapy does not add significant toxicity or alter the desired interval between cycles. The addition of brentuximab vedotin prevented relapses during therapy, and the OS and EFS estimates compare favorably with results obtained using conventional chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT01979536.
Cryo-EM structures of human coagulation factors V and Va
Authors: Ruben Eliza A. , Rau Michael J. , Fitzpatrick James A. J. , Di Cera Enrico
Published: March 2021

Coagulation factor V (fV) is the precursor of fVa, which, together with fXa, Ca2+, and phospholipids, defines the prothrombinase complex and activates prothrombin in the penultimate step of the coagulation cascade. We solved the cryogenic electron microscopy (cryo-EM) structures of human fV and fVa at atomic (3.3 Å) and near-atomic (4.4 Å) resolution, respectively. The structure of fV reveals the entire A1-A2-B-A3-C1-C2 assembly, but with a surprisingly disordered B domain. The C1 and C2 domains provide a platform for interaction with phospholipid membranes and support the A1 and A3 domains, with the A2 domain sitting on top of them. The B domain is highly dynamic and visible only for short segments connecting to the A2 and A3 domains. The A2 domain reveals all sites of proteolytic processing by thrombin and activated protein C, a partially buried epitope for binding fXa, and fully exposed epitopes for binding activated protein C and prothrombin. Removal of the B domain and activation to fVa exposes the sites of cleavage by activated protein C at R306 and R506 and produces increased disorder in the A1-A2-A3-C1-C2 assembly, especially in the C-terminal acidic portion of the A2 domain that is responsible for prothrombin binding. Ordering of this region and full exposure of the fXa epitope emerge as necessary steps in the assembly of the prothrombin-prothrombinase complex. These structures offer molecular context for the function of fV and fVa and pioneer the analysis of coagulation factors by cryo-EM.
Long-term outcomes of R-CEOP show curative potential in patients with DLBCL and a contraindication to anthracyclines
Authors: Moccia Alden A. , Schaff Kimberly , Freeman Ciara , Hoskins Paul J. , Klasa Richard J. , Savage Kerry J. , Shenkier Tamara N. , Gascoyne Randy D. , Connors Joseph M. , Sehn Laurie H.
Published: March 2021

Doxorubicin plays an integral role in the treatment of patients with diffuse large B-cell lymphoma (DLBCL) but can be associated with significant toxicity. Treatment guidelines of British Columbia (BC) Cancer recommend the substitution of etoposide for doxorubicin in standard-dose R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) (R-CEOP) for patients who have a contraindication to anthracyclines; however, it is unknown if this compromises treatment outcome. We identified all patients with newly diagnosed DLBCL who were treated in BC with curative intent with R-CEOP (n = 70) within the study period. Outcome in this population was compared with a 2:1 case-matched control group (n = 140) treated with R-CHOP and matched for age, clinical stage, and International Prognostic Index score. The 10-year time to progression and disease-specific survival were not significantly different for patients treated with R-CEOP compared with patients in the R-CHOP control group (53% vs 62% [P = .089] and 58% vs 67% [P = .251], respectively). The 10-year overall survival was lower in the R-CEOP group (30% vs 49%, P = .002), reflecting the impact of underlying comorbidities and frailty of this population. R-CEOP represents a useful treatment alternative for patients with DLBCL and an absolute contraindication to the use of anthracyclines, with curative potential.
Population pharmacokinetics of the von Willebrand factor–factor VIII interaction in patients with von Willebrand disease
Authors: Bukkems Laura H. , Heijdra Jessica M. , de Jager Nico C. B. , Hazendonk Hendrika C. A. M. , Fijnvandraat Karin , Meijer Karina , Eikenboom Jeroen C. J. , Laros-van Gorkom Britta A. P. , Leebeek Frank W. G. , Cnossen Marjon H. , Mathôt Ron A. A.
Published: March 2021

Recent studies have reported that patients with von Willebrand disease treated perioperatively with a von Willebrand factor (VWF)/factor VIII (FVIII) concentrate with a ratio of 2.4:1 (Humate P/Haemate P) often present with VWF and/or FVIII levels outside of prespecified target levels necessary to prevent bleeding. Pharmacokinetic (PK)-guided dosing may resolve this problem. As clinical guidelines increasingly recommend aiming for certain target levels of both VWF and FVIII, application of an integrated population PK model describing both VWF activity (VWF:Act) and FVIII levels may improve dosing and quality of care. In total, 695 VWF:Act and 894 FVIII level measurements from 118 patients (174 surgeries) who were treated perioperatively with the VWF/FVIII concentrate were used to develop this population PK model using nonlinear mixed-effects modeling. VWF:Act and FVIII levels were analyzed simultaneously using a turnover model. The protective effect of VWF:Act on FVIII clearance was described with an inhibitory maximum effect function. An average perioperative VWF:Act level of 1.23 IU/mL decreased FVIII clearance from 460 mL/h to 264 mL/h, and increased FVIII half-life from 6.6 to 11.4 hours. Clearly, in the presence of VWF, FVIII clearance decreased with a concomitant increase of FVIII half-life, clarifying the higher FVIII levels observed after repetitive dosing with this concentrate. VWF:Act and FVIII levels during perioperative treatment were described adequately by this newly developed integrated population PK model. Clinical application of this model may facilitate more accurate targeting of VWF:Act and FVIII levels during perioperative treatment with this specific VWF/FVIII concentrate (Humate P/Haemate P).
Survival estimates in European cystic fibrosis patients and the impact of socioeconomic factors: a retrospective registry cohort study
Authors: McKone Edward F. , Ariti Cono , Jackson Abaigeal , Zolin Anna , Carr Siobhán B. , Orenti Annalisa , van Rens Jacqui G. , Lemonnier Lydie , Macek Milan , Keogh Ruth H. , Naehrlich Lutz
Published: March 2021

Background

Median survival for cystic fibrosis (CF) patients in Europe is unknown and is likely to be influenced by socioeconomic factors. Using the European CF Society Patient Registry (ECFSPR), median survival estimates were obtained for CF patients across Europe and the impact of socioeconomic status on survival was examined.

Methods

CF subjects known to be alive and in the ECFSPR between 2010 and 2014 were included. Survival curves were estimated using the Kaplan–Meier method. Differences in the survival curves were assessed using the log-rank test. Cox regression was used to estimate the association between socioeconomic factors and the age-specific hazard of death, with adjustment for sex, age at diagnosis, CF transmembrane conductance regulator (CFTR) genotype and transplant status.

Results

The final analysis included 13 countries with 31 987 subjects (135 833 person-years of follow-up) and 1435 deaths. Median survival age for these patients in the ECFSPR was 51.7 (95% CI 50.0–53.4) years. After adjusting for potential confounders age at diagnosis, sex,CFTRgenotype and transplant status, there remained strong evidence of an association between socioeconomic factors and mortality (p<0.001). Countries in the highest third of healthcare spending had a 46% lower hazard of mortality (HR 0.54, 95% CI 0.45–0.64) than countries in the lowest third of healthcare spending.

Conclusions

Median survival for patients with CF in Europe is comparable to that reported in other jurisdictions and differs by socioeconomic factors.
Safety and efficacy of flexible and semi-rigid ureteroscopy with laser lithotripsy for the management of ureteral calculi in pregnancy
Authors: Rashid Aso Omer , Abdala Rezhin Yaseen
Published: March 2021

Background

Symptomatic ureteric stone during pregnancy can present a clinical challenge because of potential risks to both the mother and foetus. Ureteroscopy with laser and stone basket extraction represents an emerging strategy for definitive stone management in pregnancy, with minor complications. We aimed to evaluate the safety and efficacy of ureteroscopy with auxiliary procedures as a primary treatment for pregnant women with symptomatic ureteric stones who have failed conservative management.

Methods

A prospective analysis was conducted in the Urology Department of Sulaymaniyah Teaching Hospital from June 2017 to November 2019 to evaluate pregnant patients who were treated with ureteroscopy and holmium laser lithotripsy for symptomatic ureteric stone.

Results

Twenty-six pregnant women aged between 18 and 34 years presented with renal colic (22 patients, 84.61%), severe hydronephrosis (3 patients, 11.53%), and progressive hydronephrosis (1 patient, 3.8%), suggesting ureteric stones. The diagnosis was established by abdominal ultrasonography. The mean stone size was 7.38 mm, ranging from 6–12 mm. The stones were located in the proximal ureter (n = 6, 23.1%), middle ureter (n = 0), and distal ureter (n = 20, 76.9%). Complete stone fragmentation was achieved in all patients. The overall procedure success rate was 87%, the stone-free rate was 23 out of 26 cases (88.46%), and no major obstetric or urologic complications were encountered.

Conclusions

Ureteric stone in pregnancy requires a high index of suspicion for a prompt and correct diagnosis. Ureteroscopy: flexible or semirigid endoscopy combined with holmium: YAG laser lithotripsy or with stone extraction are a preferred modality for the definitive treatment of symptomatic ureteric stone in pregnancy.
Assessing the genetic background and genomic relatedness of red cattle populations originating from Northern Europe
Authors: Schmidtmann Christin , Schönherz Anna , Guldbrandtsen Bernt , Marjanovic Jovana , Calus Mario , Hinrichs Dirk , Thaller Georg
Published: March 2021

Background

Local cattle breeds need special attention, as they are valuable reservoirs of genetic diversity. Appropriate breeding decisions and adequate genomic management of numerically smaller populations are required for their conservation. At this point, the analysis of dense genome-wide marker arrays provides encompassing insights into the genomic constitution of livestock populations. We have analyzed the genetic characterization of ten cattle breeds originating from Germany, The Netherlands and Denmark belonging to the group of red dairy breeds in Northern Europe. The results are intended to provide initial evidence on whether joint genomic breeding strategies of these populations will be successful.

Results

Traditional Danish Red and Groningen White-Headed were the most genetically differentiated breeds and their populations showed the highest levels of inbreeding. In contrast, close genetic relationships and shared ancestry were observed for the populations of German Red and White Dual-Purpose, Dutch Meuse-Rhine-Yssel, and Dutch Deep Red breeds, reflecting their common histories. A considerable amount of gene flow from Red Holstein to German Angler and to German Red and White Dual-Purpose was revealed, which is consistent with frequent crossbreeding to improve productivity of these local breeds. In Red Holstein, marked genomic signatures of selection were reported on chromosome 18, suggesting directed selection for important breeding goal traits. Furthermore, tests for signatures of selection between Red Holstein, Red and White Dual-Purpose, and Meuse-Rhine-Yssel uncovered signals for all investigated pairs of populations. The corresponding genomic regions, which were putatively under different selection pressures, harboured various genes which are associated with traits such as milk and beef production, mastitis and female fertility.

Conclusions

This study provides comprehensive knowledge on the genetic constitution and genomic connectedness of divergent red cattle populations in Northern Europe. The results will help to design and optimize breeding strategies. A joint genomic evaluation including some of the breeds studied here seems feasible.
Adaptation and convergence in circadian‐related genes in Iberian freshwater fish
Authors: Moreno João M. , Jesus Tiago F. , Coelho Maria M. , Sousa Vitor C.
Published: March 2021

Background

The circadian clock is a biological timing system that improves the ability of organisms to deal with environmental fluctuations. At the molecular level it consists of a network of transcription-translation feedback loops, involving genes that activate (bmal and clock – positive loop) and repress expression (cryptochrome (cry) and period (per) – negative loop). This is regulated by daily alternations of light but can also be affected by temperature. Fish, as ectothermic, depend on the environmental temperature and thus are good models to study its integration within the circadian system. Here, we studied the molecular evolution of circadian genes in four Squalius freshwater fish species, distributed across Western Iberian rivers affected by two climatic types with different environmental conditions (e.g., light and temperature). S. carolitertii and S. pyrenaicus inhabit the colder northern region under Atlantic climate type, while S. torgalensis, S. aradensis and some populations of S. pyrenaicus inhabit the warmer southern region affected by summer droughts, under Mediterranean climate type.

Results

We identified 16 circadian-core genes in the Squalius species using a comparative transcriptomics approach. We detected evidence of positive selection in 12 of these genes using methods based on dN/dS. Positive selection was mainly found in cry and per genes of the negative loop, with 55 putatively adaptive substitutions, 16 located on protein domains. Evidence for positive selection is predominant in southern populations affected by the Mediterranean climate type. By predicting protein features we found that changes at sites under positive selection can impact protein thermostability by changing their aliphatic index and isoelectric point. Additionally, in nine genes, the phylogenetic clustering of species that belong to different clades but inhabit southern basins with similar environmental conditions indicated evolutionary convergence. We found evidence for increased nonsynonymous substitution rate in convergent lineages, likely due to positive selection at 27 sites, mostly in cry genes.

Conclusions

Our results support that temperature may be a selective pressure driving the evolution of genes involved in the circadian system. By integrating sequence-based functional protein prediction with dN/dS-based methods to detect selection we uncovered adaptive convergence in the southern populations, probably related to their similar thermal conditions.
COVID-19 infection control measures and outcomes in urban dialysis centers in predominantly African American communities
Authors: Apata Ibironke W. , Cobb Jason , Navarrete Jose , Burkart John , Plantinga Laura , Lea Janice P.
Published: March 2021

Background

Emory Dialysis serves an urban and predominantly African American population at its four outpatient dialysis facilities. We describe COVID-19 infection control measures implemented and clinical characteristics of patients with COVID-19 in the Emory Dialysis facilities.

Methods

Implementation of COVID-19 infection procedures commenced in February 2020. Subsequently, COVID-19 preparedness assessments were conducted at each facility. Patients with COVID-19 from March 1–May 31, 2020 were included; with a follow-up period spanning March–June 30, 2020. Percentages of patients diagnosed with COVID-19 were calculated, and characteristics of COVID-19 patients were summarized as medians or percentage. Baseline characteristics of all patients receiving care at Emory Dialysis (i.e. Emory general dialysis population) were presented as medians and percentages.

Results

Of 751 dialysis patients, 23 (3.1%) were diagnosed with COVID-19. The median age was 67.0 years and 13 patients (56.6%) were female. Eleven patients (47.8%) were residents of nursing homes. Nineteen patients (82.6%) required hospitalization and 6 patients (26.1%) died; the average number of days from a positive SARS-CoV-2 (COVID) test to death was 16.8 days (range 1–34). Two patients dialyzing at adjacent dialysis stations and a dialysis staff who cared for them, were diagnosed with COVID-19 in a time frame that may suggest transmission in the dialysis facility. In response, universal masking in the facility was implemented (prior to national guidelines recommending universal masking), infection control audits and re-trainings of PPE were also done to bolster infection control practices.

Conclusion

We successfully implemented recommended COVID-19 infection control measures aimed at mitigating the spread of SARS-CoV-2. Most of the patients with COVID-19 required hospitalizations. Dialysis facilities should remain vigilant and monitor for possible transmission of COVID-19 in the facility.
The construction and validation of an RNA binding protein-related prognostic model for bladder cancer
Authors: Chen Fengxia , Wang Qingqing , Zhou Yunfeng
Published: March 2021

Background

RNA-binding proteins (RBPs) play crucial and multifaceted roles in post-transcriptional regulation. While RBPs dysregulation is involved in tumorigenesis and progression, little is known about the role of RBPs in bladder cancer (BLCA) prognosis. This study aimed to establish a prognostic model based on the prognosis-related RBPs to predict the survival of BLCA patients.

Methods

We downloaded BLCA RNA sequence data from The Cancer Genome Atlas (TCGA) database and identified RBPs differentially expressed between tumour and normal tissues. Then, functional enrichment analysis of these differentially expressed RBPs was conducted. Independent prognosis-associated RBPs were identified by univariable and multivariable Cox regression analyses to construct a risk score model. Subsequently, Kaplan–Meier and receiver operating characteristic curves were plotted to assess the performance of this prognostic model. Finally, a nomogram was established followed by the validation of its prognostic value and expression of the hub RBPs.

Results

The 385 differentially expressed RBPs were identified included 218 and 167 upregulated and downregulated RBPs, respectively. The eight independent prognosis-associated RBPs (EFTUD2, GEMIN7, OAS1, APOBEC3H, TRIM71, DARS2, YTHDC1, and RBMS3) were then used to construct a prognostic prediction model. An in-depth analysis showed lower overall survival (OS) in patients in the high-risk subgroup compared to that in patients in the low-risk subgroup according to the prognostic model. The area under the curve of the time-dependent receiver operator characteristic (ROC) curve were 0.795 and 0.669 for the TCGA training and test datasets, respectively, showing a moderate predictive discrimination of the prognostic model. A nomogram was established, which showed a favourable predictive value for the prognosis of BLCA.

Conclusions

We developed and validated the performance of a prognostic model for BLCA that might facilitate the development of new biomarkers for the prognostic assessment of BLCA patients.
In-vitro glistening formation in six different foldable hydrophobic intraocular lenses
Authors: Tandogan Tamer , Auffarth Gerd U. , Son Hyeck-Soo , Merz Patrick , Choi Chul Young , Khoramnia Ramin
Published: March 2021

Background

Glistenings describe small, refractile microvacuoles that may arise within the intraocular lens (IOL) material and reduce the patients’ quality of vision. Lenses composed of hydrophobic acrylic material are particularly affected by glistening formation. In this study, we compared the tendency of glistening formation in six different types of hydrophobic acrylic intraocular lenses (IOLs).

Methods

We used a well-established accelerated laboratory method to develop glistenings in the following IOLs: Vivinex XY1 (Hoya), AcrySof SN60WF (Alcon), Tecnis ZCB00 (AMO), Avansee PN6A (Kowa), Aktis SP NS-60YG (Nidek), and CT Lucia 601P (Zeiss). IOLs were first immersed in saline at 45 °C for 24 h and then at 37 °C for 2.5 h in a water bath. Microvacuole (MV) density and size (Miyata grading) were documented and calculated using an image analysis program.

Results

The mean glistening density [MV/mm2] and mean Miyata grading (in brackets) were: Vivinex: 11.6 ± 5.7 (0), SN60WF: 264.4 ± 110.3 (2.6), Tecnis: 6.0 ± 2.8 (0), Avansee: 2.2 ± 0.7 (0), Aktis: 851.4 ± 59.4 (3+) and CT Lucia: 71.0 ± 71.6 (1).

Conclusions

While all tested IOLs showed glistenings with the accelerated laboratory method, the Aktis and SN60WF showed the highest microvacuole density, followed by the CT Lucia. In comparison, the Vivinex, Tecnis, and Avansee IOLs showed far fewer number of glistenings.