bluuebunny/crossref_metadata_2025 huggingface dataset:
Right on Schedule: Improving the Rate of Clinic Appointments Scheduled Prior to Hospital Hospital Discharge
Authors: Rahim Mahvish Q. , Griffin Jordyn , Hege Kerry , Mueller Emily L. , Kauffman Kristine , Corman Stacey , Anderson Kari , Woodburn Stayce , Jackson Meghan Drayton
Published: January 2022

Introduction:

Children with cancer and blood disorders have many healthcare needs that often require inpatient and outpatient management. There is potential for a lapse in care when patients frequently transition between these settings. We aimed to improve the process and increase the rate of scheduled outpatient follow-up appointments at the time of inpatient discharge for all pediatric hematology-oncology patients from a baseline of 68–80%.

Methods:

A multidisciplinary team developed several Plan-Do-Study-Act cycles to standardize and improve the process of scheduling follow-up appointments, communication to schedulers, and discussion of discharge planning. QI Macros for Excel Version 2019.06 was used for statistical analysis. Our primary outcome was displayed over time with a p-chart.

Results:

Plan-Do-Study-Act interventions had a statistically significant impact in increasing the percentage of patients with follow-up outpatient appointments scheduled at the time of inpatient discharge from a baseline of 68% to consistently over 80%.

Conclusions:

This study demonstrates that standardization of care processes and reminders and education of healthcare providers about the new approaches can improve the rates of outpatient follow-up appointments scheduled at the time of hospital discharge from inpatient care.
Improving Adherence to Safe Sleep Guidelines for Hospitalized Infants at a Children’s Hospital
Authors: Molina Adolfo L. , Harrison Meghan , Dye Candice , Stoops Christine , Schmit Erinn O.
Published: January 2022

Introduction:

Sudden unexpected infant deaths are a major problem nationally. We had poor adherence to safe sleep recommendations locally at our institution. Given the significance of this problem, hospital administration at a tertiary children’s hospital tasked a multidisciplinary group of faculty and staff with improving sleep environments for hospitalized infants.

Methods:

Our safe sleep task force implemented targeted interventions using the American Academy of Pediatrics policy statement as the gold standard and based on hospital data to address areas of greatest nonadherence to recommendations. We aimed to improve weekly average adherence to 95% over 12 months. A proportions process control chart (p-chart) tracked average weekly adherence over a 52-week time frame. In addition, we performed Student’s t-testing to evaluate differences in adherence over time.

Results:

There was a significant improvement in overall adherence to safe sleep recommendations from baseline (M = 70.8%, SD 21.6) to end of study period (M = 94.7%, SD 10.0) [t(427) = −15.1, P ≤ 0.001]. Crib audits with 100% adherence increased from a baseline (M = 0%, SD 0) to the end of the study period M = 70.4%, SD = 46) [t(381)= −21.4, P ≤ 0.001]. This resulted in two trend shifts on the p-chart using Institute for Healthcare Improvement control chart rules.

Conclusions:

Targeted interventions using QI methodology led to significant increases in adherence to safe sleep guidelines. Notable improvements in behavior indicated significant changes in safe sleep culture. We also noted continued adherence in follow-up audits reflecting sustainability.
Simulation-Based System Analysis: Testing Preparedness for Extracorporeal Membrane Oxygenation Cannulation in Pediatric COVID-19 Patients
Authors: Stoner Alyssa C. , Schremmer Robert D. , Miller Mikaela A. , Davidson Kari L. , Pedigo Rachael L. , Parson Jamie S. , Kennedy Christopher S. , Pallotto Eugenia K. , Miller Jenna O.
Published: January 2022

Introduction:

Coronavirus Disease-2019 presents risk to both patients and medical teams. Staff-intensive, complex procedures such as extracorporeal membrane oxygenation (ECMO) or extracorporeal cardiopulmonary resuscitation (eCPR) may increase chances of exposure and spread. This investigation aimed to rapidly deploy an in situ Simulation-based Clinical Systems Testing (SbCST) framework to identify Latent Safety Threats (LSTs) related to ECMO/eCPR initiation during a pandemic.

Methods:

The adapted SbCST framework tested systems related to ECMO/eCPR initiation in the Neonatal and Pediatric Intensive Care Units. Systems were evaluated in six domains (Resources, Processes/Systems, Facilities, Clinical Performance, Infection Control, and Communication). We conducted three high-fidelity simulations with members from the Neonatal Intensive Care Unit General Surgery, Pediatric Intensive Care Unit Cardiovascular Surgery (CV), and Pediatric Intensive Care Unit General Surgery teams. Content experts evaluated systems issues during simulation, and LSTs were identified during debriefing. Data were analyzed for frequency of LSTs and trends in process gaps.

Results:

Sixty-six LSTs were identified across three scenarios. Resource issues comprised the largest category (26%), followed by Process/System issues (24%), Infection Control issues (24%), Communication issues (17%), and Facility and Clinical Performance issues (5% each). LSTs informed new team strategies such as the use of a “door/PPE monitor” and “inside/outside” team configuration.

Conclusions:

The adapted SbCST framework identified multiple LSTs related to ECMO/eCPR cannulation and infection control guidelines in the setting of Coronavirus Disease-2019. Through SbCSTs, we developed guidelines to conserve PPE and develop optimal workflows to reduce patient/staff exposure in a high-risk procedure. This project may guide other hospitals to adapt SbCSTs strategies to test/adjust rapidly changing guidelines.
Implementing an EMR-based Health-related Social Needs Screen in a Pediatric Hospital System
Authors: Dolce Millie , Keedy Hannah , Chavez Laura , Boch Samantha , Zaim Hannah , Dias Brennan , Chisolm Deena
Published: January 2022

Introduction:

There is growing recognition of the need for effective screening methods and delivering interventions to address health-related social needs (HRSN) in hospital systems, but few studies exist on implementing such a wide-scale undertaking. This article describes the implementation and preliminary findings of a phased roll-out of an institution-wide HRSN screening.

Methods:

We describe the HRSN implementation and data tracking procedures.

Results:

During the first 13 months of the roll-out, 62,315 patient encounters from multiple clinics were eligible for screening, and 52,331 (84.0%) completed the screening. Twelve percent of patients had at least one HRSN need, and 3.5% of those had an urgent need and thus received a social work consult.

Conclusion:

Implementation of the first phase of an institution-wide HRSN screen resulted in high screening and follow-up rates among those with urgent needs, demonstrating feasibility across different clinic settings.
Sustained Reduction in Time to Data Entry in the Cystic Fibrosis Foundation Registry
Authors: Nay Laura , Vajda Jame’ , McNamara Sharon , Ong Thida
Published: January 2022

Introduction:

Timely data entry into patient registries is foundational to learning health systems such as the Cystic Fibrosis Learning Network. The US Cystic Fibrosis Foundation Patient Registry (CFFPR) is an established registry that collects encounter data for clinical and research activities. Coordinators manually enter approximately 1,500 encounters annually at our institution, but there is limited evidence for interventions facilitating timely data entry. Our institution aimed to reduce the number of days between a clinical encounter and data entry into the CFFPR from an average of 43 days (range 0 to 183 days) to less than 30 days in a 3-month interval.

Methods:

Data coordinators tested interventions to address barriers in four themes: accountability, work burden, communication, and visibility using plan-do-study-act cycles. We used statistical process control charts to assess progress on average time of entry. Coordinators provided feedback about acceptability and satisfaction for process changes.

Results:

Initial interventions standardized process and reduced average time to data entry from 42.6 to 22.5 days in 3 months, but this process was not stable in the subsequent 6 months. Subsequent changes to increase metric visibility and improve team communication increased stability and decreased the average time to data entry to 23.0 days. Coordinators reported high satisfaction with process changes and have sustained improved time for over 2 years.

Conclusions:

This quality improvement project reduced and maintained data entry time by addressing significant barriers without additional personnel. Increased access to near real-time data in CFFPR accelerates learning for clinical care, quality improvement, and research.
An extended reservoir of class-D beta-lactamases in non-clinical bacterial strains
Authors: Lupo Valérian , Mercuri Paola Sandra , Frère Jean-Marie , Joris Bernard , Galleni Moreno , Baurain Denis , Kerff Frédéric
Published: January 2022

Bacterial genes coding for antibiotic resistance represent a major issue in the fight against bacterial pathogens. Among those, genes encoding beta-lactamases target penicillin and related compounds such as carbapenems, which are critical for human health. Beta-lactamases are classified into classes A, B, C and D, based on their amino acid sequence. Class D enzymes are also known as OXA beta-lactamases, due to the ability of the first enzymes described in this class to hydrolyze oxacillin. While hundreds of class D beta-lactamases with different activity profiles have been isolated from clinical strains, their nomenclature remains very uninformative. In this work, we have carried out a comprehensive survey of a reference database of 80,490 genomes and identified 24,916 OXA-domain containing proteins. These were deduplicated and their representative sequences clustered into 45 non-singleton groups derived from a phylogenetic tree of 1413 OXA-domain sequences, including five clusters that include the C-terminal domain of the BlaR membrane receptors. Interestingly, 801 known class D beta-lactamases fell into only 18 clusters. To probe the unknown diversity of the class, we selected ten protein sequences in ten uncharacterized clusters and studied the activity profile of the corresponding enzymes. A beta-lactamase activity could be detected for seven of them. Three enzymes were active against oxacillin and two against imipenem. These results indicate that, as already reported, environmental bacteria constitute a large reservoir of resistance genes that can be transferred to clinical strains, whether through plasmid exchange or hitchhiking with the help of transposase genes.

Importance

The transmission of genes coding for resistance factors from environmental to nosocomial strains is a major component in the development of bacterial resistance towards antibiotics. Our survey of class D beta-lactamase genes in genomic databases highlighted the high sequence diversity of the enzymes that are able to recognize and/or hydrolyze beta-lactam antibiotics. Among those, we could also identify new beta-lactamases that are able to hydrolyze carbapenems, one of the last resort antibiotic families used in human chemotherapy. Therefore, it can be expected that the use of this antibiotic family will fuel the emergence of new beta-lactamases into clinically relevant strains.
K-edge anomalous SAXS for protein solution structure modeling
Authors: Virk Karman , Yonezawa Kento , Choukate Komal , Singh Lucky , Shimizu Nobutaka , Chaudhuri Barnali
Published: January 2022

K-edge anomalous SAXS intensity was measured from a small, dimeric, partly unstructured protein segment of myosin X by using cupric ions bound to its C-terminal polyhistidine tags. Energy-dependent anomalous SAXS can provide key location-specific information about metal-labeled protein structures in solution that cannot be obtained from routine SAXS analysis. However, anomalous SAXS is seldom used for protein research due to practical difficulties, such as a lack of generic multivalent metal-binding tags and the challenges of measuring weak anomalous signal at the metal absorption edge. This pilot feasibility study suggests that weak K-edge anomalous SAXS signal can be obtained from transition metals bound to terminally located histidine tags of small proteins. The measured anomalous signal can provide information about the distribution of all metal–protein distances in the complex. Such an anomalous SAXS signal can assist in the modeling and validation of structured or unstructured proteins in solution and may potentially become a new addition to the repertoire of techniques in integrative structural biology.
A bibliometric study on library and information science and information systems literature during 2010–2019
Authors: Wijewickrema Manjula
Published: January 2022

Purpose

Studying the nature of research progress in interrelated research domains is important for evaluating the research productivity and to understand the current trends of the area of research. This study aims to examine a research domain that combines library and information science with information systems (IS).

Design/methodology/approach

Quartile 1 journals that cover both subject domains in SCImago were selected for the study. Bibliographic records of the publications during 2010 and 2019 were retrieved from the Scopus database. VOSviewer data visualization tool was used to perform citation, coauthorship, bibliographic coupling, cocitation and co-occurrence analysis. In addition, descriptive and inferential statistics were exploited.

Findings

The absence of a consistent association between the number of documents authored and the number of citations received by a researcher was an important finding of the study. The strong association of authors regardless of the different topics they researched and the trend of increasing interest on collaborative research were also highlighted. Moreover, the authors who received the highest number of citations were not always the first authors of the documents which received the most citations. The documents published in information management, information theory and IS journals attained the most citations. The journals, institutions and countries with the highest number of documents and citations were also revealed by the research. Electrical engineering departments showed a higher research productivity, while they were utilized more compared to that of other departments. IS and management, information theory, communication, information retrieval, geographic-based IS and bioinformatics were the six major research areas of the considered domain.

Originality/value

This is the first study related to examining the research progress in a combined subject domain using multiple aspects including, individual performance, institutional progress, geographical contribution and so on. Identifying the major research areas in the combined subject domain can also be considered a novel contribution to the field.
Optimization of fleet structure and investment evaluation – the cargo owner's fleet perspective
Authors: Jin Zhihong , Wang Xiaohan , Sun Jiaqing , Xu Qi
Published: January 2022

Purpose

Energy groups are cargo owners with large amounts of energy sources (such as coal) to transport. To achieve a satisfactory tradeoff between the reliability requirements of the sea transportation process and the need to control the investment cost, they usually set up a self-owned fleet supplemented by a chartered fleet. This paper aims to investigate the best fleet structure and to evaluate the investment scheme under volatile circumstances in the shipping market.

Design/methodology/approach

The authors construct a mathematical model to determine the ratio of the self-owned fleet to the total fleet to minimize fleet operating costs. The volatility of both freight rates and oil prices is taken into consideration. The CPLEX solver is used to empirically analyze real data from an energy group in China, and the ship investment plan is evaluated considering the technical and economic feasibility.

Findings

If the ratio of the self-owned fleet to the total fleet is increased to the optimal of 90.40%, the total operating cost is reduced by 33.98%. Thus, the energy group should increase its capacity with a Panamax vessel of approximately 82,000 DWT. Purchasing a 5-year-old secondhand ship and building a new ship both have good investment return indicators.

Originality/value

For cargo owners engaging in transporting bulk cargo domestically in China, the suggested fleet ratio can provide a reference with a universal application scale, given the boundary economic conditions (including the volatility of freight rates and oil prices in the shipping market) in the paper.
3D high‐order sparse radon transform with L1–2 minimization for multiple attenuation
Authors: Geng Weiheng , Li Jingye , Chen Xiaohong , Ma Jitao , Xu Jiamin , Zhu Guang , Tang Wei
Published: January 2022

Among many multiple attenuation methods, parabolic Radon transform has been widely used due to its efficiency and effectiveness. However, there are two factors that restrict the application of Radon transform: (1) the smearing caused by finite seismic acquisition aperture and discrete sampling of seismic data and (2) the destruction of the amplitude versus offset signature in seismic data. Therefore, a high‐order sparse Radon transform in the mixed frequency–time domain with L1–2 minimization is proposed. The L1–2 metric has been proved an unbiased approximation to L0 norm, which helps improve the sparsity and resolution of the Radon model. By combining the orthogonal polynomial transform, which can fit the amplitude variations of seismic data, the amplitude versus offset signature is also considered. Furthermore, the 2D Radon transform is extended to 3D by modifying the augmented Lagrangian in the alternating direction method of multipliers algorithm. Compared with the 2D algorithm, 3D Radon transform considers seismic wave propagation in three dimensions, which can describe the wavefield more accurately. The proposed method is applied to multiple attenuation examples based on both synthetic and real 3D data examples to demonstrate its effectiveness, compared with some existing high‐resolution techniques and the corresponding 2D algorithm.
A dual mechanism fully blocks ethanol relapse: Role of vagal innervation
Authors: Quintanilla María Elena , Ezquer Fernando , Morales Paola , Santapau Daniela , Ezquer Marcelo , Herrera‐Marschitz Mario , Israel Yedy
Published: January 2022

Previous studies showed that vagotomy markedly inhibits alcohol self‐administration. Present studies hypothesised that vagotomy significantly adds to the inhibition of alcohol relapse induced by drugs that reduce the alcohol‐induced hyperglutamatergic state (e.g., N‐acetylcysteine + acetylsalicylic acid). The alcohol relapse paradigm tested gauges the elevated alcohol intake observed in animals that had consumed ethanol chronically, were subjected to a prolonged alcohol deprivation and are subsequently allowed ethanol re‐access. Ethanol‐drinker rats (UChB) were exposed to 10% and 20% ethanol and water concurrently for 4 months, were alcohol deprived for 14 days and were thereafter allowed re‐access to the ethanol solutions. An initial binge‐like drinking episode is observed upon ethanol re‐access, followed by a protracted elevated ethanol intake that exceeds the predeprivation intake baseline. Prior to ethanol re‐access, animals were (i) administered N‐acetylcysteine (40 mg/kg/day) + acetylsalicylic acid (15 mg/kg/day), (ii) were bilaterally vagotomised, (iii) were exposed to both treatments or (iv) received no treatments. The initial binge‐like relapse intake and a protracted elevated ethanol intake observed after repeated ethanol deprivations/re‐access cycles were inhibited by 50%–70% by the administration of N‐acetylcysteine + acetylsalicylic acid and by 40%–70% by vagotomy, while the combined vagotomy plus N‐acetylcysteine + acetylsalicylic acid treatment inhibited both the initial binge‐like intake and the protracted ethanol intake by >95% (p < 0.001), disclosing a dual mechanism of ethanol relapse and subsequent inhibition beyond that induced by either treatment alone. Future exploration into the mechanism by which vagal activity contributes to ethanol relapse may have translational promise.
Intraventricular colistin sulphate as a last resort therapy in a patient with multidrug‐resistant Acinetobacter baumannii induced post‐neurosurgical ventriculitis
Authors: Yu Xu‐Ben , Huang Yue‐Yue , Zhang Xiao‐Shan , Wang Yu‐Zhen , Shi Da‐Wei , Zhang Chun‐Hong , Chen Jie , Wang Xiao‐Rong , Lin Guan‐Yang
Published: January 2022

Limited therapeutic options exist for multidrug‐resistant/extensively drug‐resistant Acinetobacter baumannii (MDR/XDR‐Ab) meningitis/ventriculitis. A combination of intravenous and intraventricular (IVT)/intrathecal (IT) polymyxins achieves good therapeutic outcomes for cases of healthcare‐associated MDR/XDR‐Ab meningitis/ventriculitis. Colistin is commercially available as colistin sulphate and its sulphomethylated derivative. However, the effect and safety of colistin sulphate in the treatment of MDR/XDR‐Ab meningitis/ventriculitis has not been reported. We report on a 66‐year‐old male patient who developed post‐neurosurgical ventriculitis caused by MDR‐Ab. IVT concomitant intravenous colistin sulphate was used as a last‐resort antimicrobial therapy, the patient's ventriculitis was dramatically improved, and the concentrations of CSF colistin were higher than the MIC breakpoint throughout the treatment. Meanwhile, no nephrotoxicity or neurotoxicity was observed during the treatment.
Pipeline capacity and the dynamics of Alberta crude oil price spreads
Authors: Galay Gregory , Thille Henry
Published: January 2022

We investigate the effect of binding pipeline capacity on price spreads between crude oil in Alberta, Canada, and competing crude oils in export markets at the other end of the pipeline. Our goal is to determine whether these price spreads are consistent with capacity‐constrained spatial arbitrage models by estimating Markov switching models of the price spreads for both heavy and light crude oil. Our results for heavy crude oil agree with the theory: we find one regime with both a low mean and a low variance, consistent with sufficient pipeline capacity, and another regime with both a higher mean and a higher variance, consistent with constrained pipeline capacity. The difference in mean spreads between regimes then provides an estimate of the mean shadow price of capacity. Price spreads for light crude oil do not display significant differences in mean spreads across regimes, suggesting that pipeline capacity constraints are less important for this commodity. Comparing our results with pipeline capacity data, we find that tight capacity is not always associated with large price spreads.
Femtosecond laser‐assisted minimally invasive lamellar keratoplasty for the treatment of advanced keratoconus
Authors: Gao Hua , Liu Mingna , Li Na , Chen Tong , Qi Xiaolin , Xie Lixin , Shi Weiyun
Published: January 2022

Background

To evaluate the initial safety and efficacy of femtosecond laser‐assisted minimal invasive lamellar keratoplasty (FL‐MILK) for advanced keratoconus.

Methods

Twenty‐two patients (22 eyes) with advanced keratoconus were included in this prospective study. All the involved eyes underwent FL‐MILK. The femtosecond laser was used to create an intrastromal pocket with a 2.3 mm incision in the recipient cornea. Then a stromal button with a diameter of 9.0 mm and a depth of 200 μm was gently inserted into the intrastromal pocket through the 2.3 mm incision and flattened. No sutures were applied. Follow‐up was conducted for 24 months.

Results

Twenty‐two patients completed follow‐up data for 12 months, 16 patients had 24 months follow‐up. No epithelial implantation, infection or allogeneic rejection were observed during the follow‐up. Based on baseline values, postoperative 12 months values and postoperative 24 months values, clinical significantly improvement was recorded in corrected distance visual acuity (CDVA) (0.40 ± 0.18 logMAR vs. 0.30 ± 0.12 logMAR and 0.23 ± 0.13 logMAR), the anterior central corneal elevation (29.14 ± 15.33 μm vs. 14.45 ± 13.75μm and 11.38 ± 8.33 μm), and corneal higher‐order aberrations (3.536 ± 1.503 vs. 2.761 ± 1.517 and 0.994 ± 0.391). Corneal biomechanical properties in all eyes improved significantly. SP‐A1 increased from 48.64 ± 12.87 preoperatively to 87.26 ± 21.01 postoperative 12 months and 88.77 ± 18.26 postoperative 24 months; deformation amplitude (DA) decreased from 1.36 ± 0.15 preoperatively to 1.21 ± 0.12 postoperative 12 months and 1.19 ± 0.19 postoperative 24 months.

Conclusions

Initial experience suggests that this minimally invasive transplantation may be a feasible option for advanced keratoconus. A larger cohort and longer follow‐up are required to validate our results and establish long‐term safety and efficacy of the procedure.
Forced Migration and Forced Disjunctions: An Exploration of Imagination's Role in Changing Long‐Standing Cultural Identity and Lifeways
Authors: Chrostowsky MaryBeth
Published: January 2022

In this article, I show how attention to cognitive processes such as imagination can help anthropology better understand the contextual factors that influence change in long‐standing cultural identity and lifeways. Using data from a 14‐month ethnographic study among returned male Dinka Bor of Southern Sudan, I illustrate how imagination allows a forced migrant to explore alternatives, including possibilities that were previously unknown, or even thought to be impossible, before displacement. As forced migrants in my study adapted to their new environment, including major disruptions to their political, cultural, and gendered world, certain events, experiences, and scenarios were more cognitively available. These salient and easily available contextual factors are influential not only in short‐term solutions but also in the reconstruction of identity and imagined futures. This empirical case shows a pattern among some male Dinka Bor forced migrants who appear to subscribe to a newly developing Dinkahood that includes an understood urbane lifestyle and an imagined future that differs from customary Dinka Bor identity and lifeways.
Establishing tourism sustainability in a globally important agricultural heritage system in China: A case of social and eco‐system recovery
Authors: Fuller Anthony M. , Bao Jigang , Liu Yi , Zhou Xiaoyi
Published: January 2022

This paper in the form of a narrative, contributes an account of revitalizing sustainability of a World Heritage site—the Hani rice‐fish terrace system—in a pristine area of cultural and ecological significance in Southwest China. Rice‐fish farming in mountain terraces is an ingenious system that has existed in various forms for hundreds of years. However, due to international recognition by FAO and UNESCO of this area as a world agricultural heritage site, the system was threatened of losing its eco‐social balance because of mass tourism overload. Remarkably, after a period of development chaos and because of changing actors and roles, a semblance of sustainability has been regained through firm protection and management of the chief tourism asset—the rice terraces. Utilising a stakeholder approach to form multiple narratives, our research reveals the interplay of government, private enterprise, Hani people and outside experts in reshaping the trajectory of tourism development when the world‐heritage attractiveness brings new threats to the ecological systems and turned the destination into a challenging geographical environment. It demonstrates the need for strong and inclusive management techniques some of which have now been applied in the core Hani area, with appreciable success.
Influence of blood group and von Willebrand factor on population pharmacokinetics and dose individualization of recombinant factor VIII in Taiwanese patients with haemophilia A
Authors: Singkham Noppaket , Punyawudho Baralee , Yu Ming‐Sun , Cheng Shin‐Nan , Chen Shu‐Huey , Chang Hung , Chen Chih‐Cheng , Hsiao Chih‐Cheng , Hou Jen‐Yin , Fang Yi‐Ping , Wang Hsiang‐Wei , Lin Jia‐Hong , Yu Lennex Hsueh‐Lin , Chen Yeu‐Chin
Published: January 2022

Introduction

The large interpatient variability in the pharmacokinetic (PK) parameters of recombinant Factor VIII (rFVIII) observed in haemophilia A hinders efficient and cost‐beneficial prophylactic regimen initiation. Identification of factors influencing the PK of rFVIII may shed more light on personalised treatment.

Aim

This study aimed to develop a population PK model in the Taiwanese haemophilia A and evaluate the current national health insurance (NHI) reimbursement guidelines of Taiwan for haemophilia treatment.

Methods

A population PK analysis was established based on 69 Taiwanese with moderate or severe haemophilia A. A nonlinear mixed‐effects modelling (NONMEM®) was used to estimate PK parameters and their variabilities. A Monte Carlo simulation was performed to evaluate different prophylactic regimens.

Results

A two‐compartment model with first‐order elimination best described the rFVIII data. Weight‐based allometric scaling was related to clearance and central volume of distribution. Blood type and baseline von Willebrand factor (VWF) were significant covariates for clearance. For single dose simulations, a time achieving target level (> 1 IU/dL) was associated with increasing rFVIII dose and VWF level. The multiple dose simulations showed that > 96.4% of patients with high VWF level (> 200%) had predicted trough level > 1 IU/dL for all dosing regimens (15‐40 IU/kg, two to three times weekly). However, for twice weekly dosing, lower percentage (47.62‐62.20%) of patients with blood group O and low VWF level (< 50%) achieved a predicted trough level > 1 IU/dL.

Conclusion

The population PK of rFVIII was successfully developed. Dose adjustment based on blood type and VWF level should be considered.
P‐Loop mutations—Negative prognosticators in tyrosine kinase inhibitors resistant chronic myeloid leukemia patients
Authors: Kaleem Bushra , Shahab Sadaf , Zaidi Uzma , Shamsi Tahir Sultan
Published: January 2022

Introduction

P‐Loop mutations in CML patients prevent the conformational change in BCR‐ABL1 necessary for drug binding. The present study aimed to evaluate the impact of mutations in this domain on the prognosis of the disease and also to associate the baseline Sokal relative risk score with the overall survival in non‐responding CML patients.

Methods

Blood samples were analyzed using ARMS‐PCR and then an association was assessed between presence/absence of mutations, hematological and molecular response, disease progression, overall survival, and Sokal score.

Results

Of the total 250 CML patients, 102 were found to be treatment‐resistant. Fifty‐three patients harbored P‐Loop mutations with G250E (12.7%) being most frequent. Complete hematological response and major molecular response were achieved by only 27.7% and 5.7 patients, respectively. Worst survival (57.1%) was observed in Y253H positive patients while according to Sokal score in high‐risk patients harboring Y253F (50%) and E255V (50%).

Conclusion

The presence of P‐Loop domain mutations negatively impacted the prognosis of the disease in terms of disease advancement and overall survival. So, the timely performance of the BCR‐ABL1 mutational analysis and the modifications in the treatment plan based on the mutation identified would help in a better outcome of the disease.
The Holy Spirit and the Humanity of Christ in John Owen: A Re‐Examination
Authors: Kieser Ty
Published: January 2022

This article re‐examines John Owen’s construal of the Holy Spirit’s activity in the humanity of Christ. While Owen’s ‘Spirit Christology’ is both lauded as exemplary and criticized as nearly Nestorian, both positions are largely based on a shared (yet faulty) assumption regarding the key text of Owen’s ‘Spirit Christology’ (Pneumatologia 3:159–88; esp. pp. 160–1). In order to correct this assumption, this article examines the claims that Owen makes in this section of Pneumatologia within three different contexts: (1) Owen’s historical context; (2) the context of Owen’s broader corpus; and (3) the immediate context of these claims within the structure and argumentation of Pneumatologia as a whole. I suggest that this rereading of Owen’s Spirit Christology is able to retain many of the desirable theological implications of the original interpretation without the same theological difficulties.
The contribution of intraspecific trait variation to changes in functional community structure along a stress gradient
Authors: Kitagawa Ryo , Masumoto Shota , Kaneko Ryo , Uchida Masaki , Mori Akira S.
Published: January 2022

Question

We considered two possibilities related to the contribution of intraspecific trait variation (ITV) to changes in functional community structure along a stress gradient in tundra vegetation. First, ITV could contribute to the success of plant species across the stress gradient by promoting optimal trait values for each condition along the gradient; thus, ITV enhances convergence toward optimal traits. Second, ITV of only a few dominant species aligns with the optimal trait, and ITV of other species promotes trait diversification within communities.

Location

Salluit, Québec, Canada (62°12′N, 75°39′W).

Methods

Vegetation was surveyed under three different conditions (harsh, intermediate, and competitive) representing an environmental stress gradient. We assessed ITV across the gradient for four plant functional traits: leaf carbon (C) and nitrogen (N) contents, specific leaf area (SLA), and plant height. We assessed community‐weighted means (CWMs) and functional dispersion (FDis) for each of the four traits. These indices were calculated from mean trait values from all individuals across all habitats (mean‐CWM and mean‐FDis), and from each habitat (ITV‐CWM and ITV‐FDis).

Results

For the four traits, increasing trends (leaf N content, SLA, and plant height) and decreasing trends (leaf C content) in mean‐CWM along the stress gradient were maintained and pronounced for ITV‐CWM. Comparisons between ITV‐FDis and mean‐FDis suggested that, except for leaf C content, ITV tends to reduce and increase FDis values at the abiotically stressful and competitive ends of the environmental stress gradient, respectively.

Conclusions

ITV along the abiotic stress–competition gradient appears to promote community‐level changes towards optimal traits. In particular, ITV in three traits (with the exception of leaf C content) may contribute to equalization of optimal trait values, and to “passage through environmental filtering” in harsh habitats. However, when species deal with competition for richer resources, only some dominant species may show optimal trait values. Therefore, ITV may allow for trait diversification within communities under competitive rather than harsh abiotic conditions.
Updates and new reports for the Flora of southern Somalia and north‐eastern Kenya (with a note on Blepharis kenyensis)
Authors: Baldesi Giacomo , Baldini Riccardo Maria , Pignotti Lia
Published: January 2022

Based on the collections held at herbarium FT, new and noteworthy records of vascular plants are provided for the flora of southern Somalia and north‐eastern Kenya. One taxon, Polycarpaea somalensis is recorded as new for the flora of Kenya. Nine taxa, Cyanotis aff. foecunda, Blepharis kenyensis, Launaea sarmentosa, Jatropha hildebrandtii var. hildebrandtii, Scaevola taccada, Polygala aff. muratii, Portulaca coralloides, Portulaca oblonga, Grewia glandulosa are recorded as new for the flora of Somalia and the presence of four taxa, Aneilema lamuense, Ehretia bakeri, Ipomoea aitonii, Strychnos decussata, previously known from single collections, is confirmed. New distributional or noteworthy records are reported for 16 species (Dyschoriste bayensis, Kleinia grantii, Pluchea sarcophylla, Vernonia bayensis, Maerua angolensis subsp. angolensis, Polycarpaea somalensis, Ipomoea kotschyana, Euphorbia hirta, Jatropha stuhlmannii, Lobelia fervens subsp. fervens, Flueggea leucopyrus, Digitaria macroblephara, Portulaca commutata, Talinum portulacifolium, Melhania kelleri, Corchorus aestuans) and for the recently described Emilia corallina one additional record is provided. A note on capsule and seed morphology of Blepharis kenyensis is included.
Dynamics of nonstructural carbohydrates in a deciduous woody species from tropical dry forests under recurrent water deficit
Authors: Santos Mariana , Nicodemos Joana , Santos Mauro G.
Published: January 2022

In tropical dry forests, both the dry and the short rainy seasons have become increasingly irregular. This study replicated these conditions to investigate the effects of two water deficit cycles on Cenostigma microphyllum seedlings. Impacts were assessed by measuring growth traits, water relations, gas exchange, and dynamics of nonstructural carbohydrate (NSC) content in the whole plant under greenhouse conditions in potted plants. In the first water deficit cycle, the leaf relative water content (RWC) was maintained at the expense of a rapid drop in gas exchange. Furthermore, there was a slight accumulation of NSC, mainly soluble sugars (SS) in the stem wood and roots, to the detriment of height and stem diameter growth. In the second cycle, the leaf RWC remained 40% higher than the lowest level measured in the first water deficit, and CO2 assimilation remained twice as long in previously stressed plants. The SS content of the stems and roots was strongly correlated with the predawn leaf RWC. No strong reduction was observed in the bark stock even with the gradual increase of SS in the wood. Our data suggest that under recurrent water deficit prior to leaf drop, CO2 assimilation is maintained, with the highest possible leaf RWC, under reduced stomatal conductance. This assists in SS transport to wood and root, which is no longer used to support the growth of the aboveground parts.
In the Semi‐Shadow of the Global West: Moroccan zawāyā as Good Public Administration
Authors: Chafik Salah , Drechsler Wolfgang
Published: January 2022

The 2020 international protests addressing structural racism and colonial legacies have also questioned Western ascendancy on defining (good) governance. Non‐Western traditional forms of governance surviving today, despite not receiving much academic attention, pose an obvious alternative. This study analyses key indigenous institutions in Morocco known as zawāyā, and in doing so, fills some of the lacunae on Islamic‐African public administration. Drawing from novel data collected via ethnographic fieldwork across three domains of public service provision, the authors, apparently for the first time in such a context, present a public administration that is functional in its operation, delivering on its goals, and on both counts markedly different from the global‐Western mainstream. Our results uncover a public administration that (1) coexists with a larger state, (2) delivers coproduced services, and (3) merits recognition.
MAT‐Index: An index for fast multiple aspect trajectory similarity measuring
Authors: de Souza Ana Paula Ramos , Renso Chiara , Perego Raffaele , Bogorny Vania
Published: January 2022

The semantic enrichment of mobility data with several information sources has led to a new type of movement data, the so‐called multiple aspect trajectories. Comparing multiple aspect trajectories is crucial for several analysis tasks such as querying, clustering, similarity, and classification. Multiple aspect trajectory similarity measurement is more complex and computationally expensive, because of the large number and heterogeneous aspects of space, time, and semantics that require a different treatment. Only a few works in the literature focus on optimizing all these dimensions in a single solution, and, to the best of our knowledge, none of them proposes a fast point‐to‐point comparison. In this article we propose the Multiple Aspect Trajectory Index, an index data structure for optimizing the point‐to‐point comparison of multiple aspect trajectories, considering its three basic dimensions of space, time, and semantics. Quantitative and qualitative evaluations show a processing time reduction of up to 98.1%.
Humoral immunity of BBIBP‐CorV (Sinopharm) in kidney transplant recipients: Is it time to revise vaccination strategies
Authors: Nafar Mohsen , Chehrazi Saghar , Dalili Nooshin , Firouzan Ahmad , Poorrezagholi Fatemeh , Samadian Fariba , Samavat Shiva
Published: January 2022

Background

The mortality of coronavirus disease 2019 (COVID‐19) is high in transplant patients, and effective vaccination is aimed to reduce severe disease and mortality.

Methods

We conducted a cross‐sectional study to evaluate humoral and cellular response to two 4‐μg doses of BBIBP‐CorV vaccine in 100 kidney transplant recipients, using anti‐spike IgG, total anti‐receptor‐binding domain, neutralizing antibody (Ab) level (enzyme‐linked immunoassay), and interferon‐gamma release assay (IGRA).

Results

Seroconversion was evaluated 85.84 ± 30.72 days after the second dose. Note that, 58% of all and 43.05% of infection‐naïve participants have developed at least one of the tested antibodies. IGRA was positive in 30.7% of tested transplant recipients. Sixty percent of the participants had either humoral or cellular responses to COVID‐19. Only age was independently linked to seropositivity of any degree after vaccination (p < .05). COVID‐naïve patients older than 60 years developed significantly less neutralizing Abs. (p = .011). Six patients developed mild COVID infection more than a month after the second dose of the vaccine (54.5 ± 20.8 days). No vaccine‐related adverse effects were reported, except self‐limited mild to moderate fever and injection site pain.

Conclusion

BBIBP‐CorV vaccine can be used safely in kidney transplant recipients, although impaired cellular and humoral immunity necessitate adjustments in vaccination strategies, like higher (8‐μg doses), fourth booster dose, or boost with different platform vaccine.
Two independent cis‐acting elements are required for the guard cell‐specific expression of SCAP1, which is essential for late stomatal development
Authors: Moriwaki Kosuke , Yanagisawa Shuichi , Iba Koh , Negi Juntaro
Published: January 2022

Regulating the stomatal aperture to adapt to environmental changes is critical for plants as stomatal guard cells are responsible for gas exchange between plants and the atmosphere. We previously showed that a plant‐specific DNA‐binding with one finger (Dof)‐type transcription factor, SCAP1, functions as a key regulator in the final stages of guard cell differentiation. In the present study, we performed deletion and gain‐of‐function analyses with the 5′ flanking region of SCAP1 to identify the regulatory region controlling the guard cell‐specific expression of SCAP1. The results revealed that two cis‐acting elements, 5′‐CACGAGA‐3′ and 5′‐CACATGTTTCCC‐3′, are crucial for the guard cell‐specific expression of SCAP1. Consistently, when an 80‐bp promoter region including these two cis‐elements was fused to a gene promoter that is not active in guard cells, it functioned as a promoter that directed gene expression in guard cells. Furthermore, the promoter region of HT1 encoding the central regulator of stomatal CO2 signaling was also found to contain a 5′‐CACGAGA‐3′ sequence, which was confirmed to function as a cis‐element necessary for guard cell‐specific expression of HT1. These findings suggest the existence of a novel transcriptional regulatory mechanism that synchronously promotes the expression of multiple genes required for the stomatal maturation and function.
Police Violence Against Black Protesters: A Public Health Issue
Authors: Anderson James F. , Lee Tazinski P. , Langsam Adam H. , Reinsmith-Jones Kelley
Published: January 2022

With the increased number of documented cases of violence perpetrated by police against protesters of the Black Lives Matter movement, public health officials are starting to list police violence as a health risk or a public health issue for black Americans. Using several timely theoretical explanations, we explore reasons why law enforcement officers routinely inflict violence against black protesters and avoid criminal stigma. Although police use of excessive force and untimely killings of blacks have always been criminal justice issues, the number of negative health consequences that are emerging after violent police confrontations implicates public health concerns. We argue that several strategies can be used to reduce police violence in the future.
Augmented ERAD (ER-associated degradation) activity in chondrocytes is necessary for cartilage development and maintenance
Authors: Sim Hyo Jung , Cho Chanmi , Kim Ha Eun , Hong Ju Yeon , Song Eun Kyung , Kwon Keun Yeong , Jang Dong Gil , Kim Seok-Jung , Lee Hyun-Shik , Lee Changwook , Kwon Taejoon , Yang Siyoung , Park Tae Joo
Published: January 2022

Chondrocytes secrete massive extracellular matrix (ECM) molecules that are produced, folded, and modified in the endoplasmic reticulum (ER). Thus, the ER-associated degradation (ERAD) complex—which removes misfolded and unfolded proteins to maintain proteostasis in the ER— plays an indispensable role in building and maintaining cartilage. Here, we examined the necessity of the ERAD complex in chondrocytes for cartilage formation and maintenance. We show that ERAD gene expression is exponentially increased during chondrogenesis, and disruption of ERAD function causes severe chondrodysplasia in developing embryos and loss of adult articular cartilage. ERAD complex malfunction also causes abnormal accumulation of cartilage ECM molecules and subsequent chondrodysplasia. ERAD gene expression is decreased in damaged cartilage from patients with osteoarthritis (OA), and disruption of ERAD function in articular cartilage leads to cartilage destruction in a mouse OA model.
Targeting mechanosensitive endothelial TXNDC5 to stabilize eNOS and reduce atherosclerosis in vivo
Authors: Yeh Chih-Fan , Cheng Shih-Hsin , Lin Yu-Shan , Shentu Tzu-Pin , Huang Ru-Ting , Zhu Jiayu , Chen Yen-Ting , Kumar Sandeep , Lin Mao-Shin , Kao Hsien-Li , Huang Po-Hsun , Roselló-Sastre Esther , Garcia Francisca , Jo Hanjoong , Fang Yun , Yang Kai-Chien
Published: January 2022

Although atherosclerosis preferentially develops at arterial curvatures and bifurcations where disturbed flow (DF) activates endothelium, therapies targeting flow-dependent mechanosensing pathways in the vasculature are unavailable. Here, we provided experimental evidence demonstrating a previously unidentified causal role of DF-induced endothelial TXNDC5 (thioredoxin domain containing 5) in atherosclerosis. TXNDC5 was increased in human and mouse atherosclerotic lesions and induced in endothelium subjected to DF. Endothelium-specific
Txndc5
deletion markedly reduced atherosclerosis in
ApoE
−/−
mice. Mechanistically, DF-induced TXNDC5 increases proteasome-mediated degradation of heat shock factor 1, leading to reduced heat shock protein 90 and accelerated eNOS (endothelial nitric oxide synthase) protein degradation. Moreover, nanoparticles formulated to deliver
Txndc5
-targeting CRISPR-Cas9 plasmids driven by an endothelium-specific promoter (
CDH5
) significantly increase eNOS protein and reduce atherosclerosis in
ApoE
−/−
mice. These results delineate a new molecular paradigm that DF-induced endothelial TXNDC5 promotes atherosclerosis and establish a proof of concept of targeting endothelial mechanosensitive pathways in vivo against atherosclerosis.