bluuebunny/crossref_metadata_2025 huggingface dataset:
CDK5 inhibition improves glucose uptake in insulin‐resistant neuronal cells via ERK1/2 pathway
Authors: Manglani Kapil , Dey Chinmoy S.
Published: December 2021

Role of CDK5 and its inhibition in various neuronal processes and functions are well established. However, role of CDK5 and its inhibition in neuronal insulin—signaling and—resistance is not yet explored. In the present study, we investigated the effect of CDK5 inhibition in neuronal insulin signaling, specifically insulin‐stimulated glucose uptake. CDK5 expression in neuro‐2a cells was increased under insulin‐resistant state, developed by chronic treatment of insulin, confirming the crucial role of CDK5 in insulin resistance in neuronal cells. However, whether increased expression of CDK5 in hyperinsulinemia‐mediated insulin‐resistant conditions is a cause or a consequence, is still an unanswered question. We showed that CDK5 inhibition did not affect basal insulin signaling; however, insulin‐stimulated glucose uptake enhanced in insulin‐resistant cells. Moreover, CDK5 inhibition could improve glucose uptake, the ultimate outcome of insulin signaling, in insulin‐resistant neuro‐2a cells. We first time showed that CDK5 inhibition by roscovitine could ameliorate insulin resistance and increase glucose uptake in neuronal cells via ERK1/2 pathway. Our study provides intriguing insights about the effect of CDK5 inhibition on neuronal insulin resistance and opens up a new paradigm to develop new therapeutic strategies for neuronal insulin resistance and associated pathophysiological conditions.
Five‐year follow‐up report: Box lesion radiofrequency ablation procedure for atrial fibrillation under video‐assisted thoracoscope
Authors: Ji Yupeng , He Li , Cheng Zeyi , Shi Jun , Liu Lulu , Guo Yingqiang
Published: December 2021

We report the initial 5‐year follow‐up of a novel mini‐invasive procedure for epicardial ablation for the treatment of atrial fibrillation. The initial 5‐year survival rate is acceptable and comparable with that of hybrid ablation. And this shared procedure has the advantages of shorter operation time and less surgical trauma.
Novel compound heterozygous mutations in the CYP4F22 gene in a patient with autosomal recessive congenital ichthyosis
Authors: Tang Haiyan , Shi Xiaoliu , Zhang Guiying
Published: December 2021

Autosomal recessive congenital ichthyosis (ARCI) is a rare form of keratinization disorder of the skin, which can be caused by mutations in 14 ARCI genes. We present a rare case of ARCI that carried a novel null mutation and a novel splice site mutation in the CYP4F22 gene.
Sinonasal immunoglobin G4—related disease: case report and review
Authors: Wilson Caleb P. , Brownlee Benjamin P. , El Rassi Edward T. , McKinney Kibwei A.
Published: December 2021

Immunoglobin G4—related disease (IgG4‐RD) is a chronic fibro‐inflammatory condition that presents as a single or multiple tumefactive lesions affecting virtually any organ system. Here we report a case of recurrent sinonasal IgG4‐RD and review the literature of this evolving entity.
Clinical course involving thrombocytosis and thrombocytopenia in a patient with bladder cancer treated with gemcitabine and cisplatin
Authors: Watanabe Ayako , Momo Kenji , Tanaka Katsumi , Nagata Takuya , Kuchira Remi , Morita Masashi , Sasaki Tadanori
Published: December 2021

Gemcitabine induce thrombocytopenia and thrombocytosis as toxicity. In this report, we show detailed time‐course for platelet fluctuation. Our case emphasis attention to monitor see‐saw‐like toxicity on platelet count.
Perceval sutureless aortic valve replacement after ascending aortic replacement
Authors: Yajima Shin , Satoh Ayaka , Sekiya Naosumi , Yamazaki Sachiko , Uemura Hisashi , Tanaka Hiroe , Yamamura Mitsuhiro , Sakaguchi Taichi
Published: December 2021

In patients with a narrow sinotubular junction, small sinus of Valsalva, or extensibility loss in the aortic root, aortic valve replacement (AVR) with a standard valve is challenging due to limited surgical field. Detailed preoperative measurements of the aortic root render performing AVR using the Perceval valve easy.
Lemierre’s syndrome caused by Fusobacterium necrophorum complicated with multiple brain abscesses—A case report, literature review, and suggested management
Authors: Kjellberg Anders , Bjerin Olof , Franzén‐Röhl Elisabeth , Bartek Jiri , Lindholm Peter
Published: December 2021

We present an unusual case of Lemierre´s syndrome complicated by multiple brain abscesses, a literature review and suggested management. A young man with multiple brain abscesses deteriorated despite two weeks of directed antibiotics. A multidisciplinary approach was successful. Hyperbaric oxygen treatment (HBOT) should be considered in refractory or severe cases.
Normoglycemic diabetic ketoacidosis in a type 2 diabetes patient on dapagliflozin: A case report
Authors: Matli Venkata Vinod Kumar , Fariduddin Maria M. , Asafo‐Agyei Kwabena Oppong , Bansal Nidhi
Published: December 2021

A 48‐year‐old male patient with Type 2 diabetes mellitus(T2D), on insulin replacement therapy, glipizide, and dapagliflozin presented with generalized weakness with weight loss of 40 pounds in 6 months ever since he was started on dapagliflozin. He was hemodynamically stable on arrival with a finger stick glucose of 121 gm%. Physical examination was unremarkable except for dry mucus membranes. His laboratory results on arrival are shown in Table 1. His serum osmolar gap was within the normal range. He was treated insulin drip per DKA protocol and gap was closed, the patient was clinically and biochemically back to baseline, and he was discharged home. Delayed diagnosis of normoglycemic diabetic ketoacidosis (DKA) in adults with diabetes treated with multiple antidiabetic drugs (eg, sodium‐glucose cotransporter‐2 [SGLT‐2] inhibitors) can potentially increase morbidity and mortality. Patient education in terms of symptoms and signs, physician awareness of early recognition of ketoacidosis in the setting of paradoxically normal or near‐normal blood glucose levels in these patients is the primary focus of this case study. This is paradoxical DKA because theoretically patient is not meeting one of the criteria for DKA which include triad of hyperglycemia, Ketoacidosis with widened anion gap, Ketonemia. This is a short case report of presumed SGLT‐2 inhibitor euglycemic diabetic ketoacidosis. The main teaching point is recognition and early diagnosis of this issue when multiple diabetic medications are present with the absence of hyperglycemia. This is, by current definition, not DKA because theoretically, the patient does not meet one of the criteria for DKA as the patient was apparently not hyperglycemic, albeit with, ketoacidosis and widened anion gap. (ketonemia)
Acute lower limb ischemia in an ICU admitted patient diagnosed with the COVID‐19: A case report
Authors: Sadeghi Armin , Moselmi Mohammadreza
Published: December 2021

Thromboembolic events have been reported in the hospitalized patient since the beginning of the COVID‐19 pandemics. ICU‐admitted patients demonstrated a significantly higher risk of developing VTE. Although evidence of arterial thrombosis was less common in ICU‐admitted patients, consequences were typically more severe, including limb loss and death. This study reports another ICU‐admitted patient with lower extremity arterial thrombosis diagnosed with COVID‐19.
A successful pediatric case of vaginal foreign body detection on transabdominal ultrasonography
Authors: Nishiyama Kazutaka , Horikawa Shogo , Ono Yusuke
Published: December 2021

Vaginal foreign bodies usually present with bleeding and foul‐smelling discharge. It is often difficult to detect and identify vaginal foreign bodies in pediatric cases without any symptoms. Therefore, detection of vaginal foreign bodies using noninvasive methods, like transabdominal ultrasonography, is important in pediatric patients.
Confined placental mosaicism of trisomy 6 detected through genome‐wide NIPT was associated with placental abruption
Authors: Nishiyama Miyuki , Wada Seiji , Hasegawa Fuyuki , Uehara Yohji , Ozaki Mamoru , Hata Kenichiro , Ito Yushi , Sago Haruhiko
Published: December 2021

Confined placental mosaicism (CPM) leads to discordant noninvasive prenatal testing (NIPT) results. We describe a very rare case of CPM of trisomy 6 detected through genome‐wide NIPT. This case was associated with placental abruption, which might suggest an association between certain types of CPM detected by NIPT and pregnancy complications.
Spontaneous pneumomediastinum mimicking acute pericarditis
Authors: Chaudhary Haseeb , Yousaf Zohaib , Nasir Usama , Waheed Tayyab , Syed Khezar
Published: December 2021

ST elevations on electrocardiogram (ECG) have a broad differential diagnosis that can vary from benign to more ominous pathologies. These include early repolarization, coronary vasospasm, acute pericarditis, ST‐elevation myocardial infarction, ventricular aneurysms, and dissecting aneurysm of the aorta reaching the pericardium. ST‐segment changes may also provide a clue to the presence of spontaneous pneumomediastinum (SPM). These ECG changes are seldom reported in literature. We describe two SPM cases with concomitant pneumopericardium that closely mimicked acute pericarditis with a deceptive clinical spectrum.
A rare and distinct bilateral ovarian tumor: Carcinosarcoma
Authors: Limaiem Faten , Halouani Ahmed , Saffar Khalil , Bouraoui Saâdia
Published: December 2021

Carcinosarcomas are aggressive biphasic neoplasms composed of high‐grade, malignant, epithelial, and mesenchymal elements. They usually occur in the uterus and rarely involve the ovaries. Only 10% of them are bilateral. Their diagnosis relies on histological examination coupled with immunohistochemistry.
Inguinal hernia detected using radiography
Authors: Takashima Yoshito , Suda Tsuyoshi , Soga Shingo
Published: December 2021

There are various clinical presentations of inguinal hernia. Computed tomography is a well‐known tool to help diagnose inguinal hernia; however, radiographs are rarely reported to be useful in this aspect. We present a rare case wherein radiographs helped in the diagnosis of inguinal hernia.
Secondary hemophagocytic lymphohistiocytosis due to nivolumab/ipilimumab in a renal cell cancer patient—A case report
Authors: Masood Adeel , Wahab Ahsan , Clifford Tanya , Weaver Eric J. , Ehsan Hamid , El Ayass Walid
Published: December 2021

Secondary immune‐related hemophagocytic lymphohistiocytosis is a rare but life‐threatening complication of immune checkpoint inhibitors. HLH‐2004 and HLH‐1994 guidelines originally developed for primary HLH are the only available guidelines. It has proven to have a good prognosis if diagnosed promptly with discontinuation of immunotherapy and treated with corticosteroid monotherapy.
Leukocyte chemotactic factor 2–related amyloidosis presenting with severe jaundice and hepatic encephalopathy
Authors: Almasri Hussam , Razok Almurtada , Badi Ahmed , Almohannadi Muneera , Lutf Abdo , Petkar Mahir , Elzouki Abdelnaser
Published: December 2021

Amyloidosis is a well‐known disease with various types and subtypes. One of the most recently identified types is leukocyte chemotactic factor 2 amyloidosis (LECT 2), which was found to be common in certain ethnic backgrounds. It is suggested that the diagnosis of this type is vital to prevent any therapy‐related complications when it is erroneously diagnosed as AL amyloidosis. The clinical presentation is usually slowly progressive kidney disease and mild hepatic impairment. We report a case of LECT2 amyloidosis, which presented with severe painless cholestasis and hepatic encephalopathy alongside progressive kidney disease.
Integrated Water Treatment System for Peat Water Treatment
Authors: Khayan Khayan , Sutomo Adi Heru , Rasyid Ashari , Puspita Widyana Lakshmi , Hariyadi Didik , Anwar Taufik , Wardoyo Slamet , Sahknan Raja , Aziz Alkausyari
Published: December 2021

The supply of clean water is a major problem in both developed and developing countries. The abundant amount of peat water can be a potential source of clean water in areas with peatlands. Peat water treatment can be conducted effectively and efficiently by integrating various existing methods, such as aeration, sedimentation, and filtration using shell sand and activated carbon. The results show that the parameters of color, turbidity, Ferrum (Fe), microbiological parameters, and pH of peat water can be conditioned according to clean water standards. The average peat watercolor parameter before processing is 866.7 PtCo, 10.96 NTU turbidity, 2.48 mg L–1Fe, Fe, 4.30 pH, and coliform (microbial) peat water at 1068 CFU and after passing the color combination treatment to 28.83 PtCo, turbidity 2.19 NTU, Fe 0.22 mg L–1, and coliform 20 CFU and pH 6.83. Integrated peat water treatment is the most effective at the filtration and adsorption stages.
Projection‐based model reduction for the immersed boundary method
Authors: Luo Yushuang , Li Xiantao , Hao Wenrui
Published: December 2021

Fluid–structure interactions are central to many biomolecular processes, and they impose a great challenge for computational and modeling methods. In this paper, we consider the immersed boundary method (IBM) for biofluid systems, and to alleviate the computational cost, we apply reduced‐order techniques to eliminate the degrees of freedom associated with the large number of fluid variables. We show how reduced models can be derived using Petrov–Galerkin projection and subspaces that maintain the incompressibility condition. More importantly, the reduced‐order model (ROM) is shown to preserve the Lyapunov stability. We also address the practical issue of computing coefficient matrices in the ROM using an interpolation technique. The efficiency and robustness of the proposed formulation are examined with test examples from various applications.
Automating fractional flow reserve (FFR) calculation from CT scans: A rapid workflow using unsupervised learning and computational fluid dynamics
Authors: Chakshu Neeraj Kavan , Carson Jason M. , Sazonov Igor , Nithiarasu Perumal
Published: December 2021

Fractional flow reserve (FFR) provides the functional relevance of coronary atheroma. The FFR‐guided strategy has been shown to reduce unnecessary stenting, improve overall health outcome, and to be cost‐saving. The non‐invasive, coronary computerised tomography (CT) angiography‐derived FFR (cFFR) is an emerging method in reducing invasive catheter based measurements. This computational fluid dynamics‐based method is laborious as it requires expertise in multidisciplinary analysis of combining image analysis and computational mechanics. In this work, we present a rapid method, powered by unsupervised learning, to automatically calculate cFFR from CT scans without manual intervention.
Deep long and short term memory based Red Fox optimization algorithm for diabetic retinopathy detection and classification
Authors: Pugal Priya Raju , Saradadevi Sivarani Thankamony , Gnana Saravanan Athimoolam
Published: December 2021

Because of retina abnormalities of diabetic patients, the most common vision‐threatening disease is diabetic retinopathy (DR). The DR diagnosis and prevention are challenging tasks as they may lead to vision loss. According to the literature analysis, the shortcomings in existing studies, such as failed to reduce the feature dimension, higher execution time, and higher computational cost, unable to tune the hyper‐parameters, such as a number of hidden layers and learning rate, more computational complexities, higher cost, and so forth, during DR classification. To tackle these problems, we proposed a deep long‐ and short‐term memory (LSTM) in a neural network with Red Fox optimization (deep LSTM‐RFO) algorithm for DR classification. The four major components involved in the proposed methods are image preprocessing, segmentation, feature extraction, and classification. At first, an adaptive histogram equalization and histogram equalization model performs the fundus image preprocessing, thereby neglecting the noise and improving the contrast level of an image. Next, an adaptive watershed segmentation model effectively segments the lesion region based on the optic disc color and size of hemorrhages. At the third stage, we have extracted statistical, intensity, color, and shape features. Finally, the single normal class with three abnormal classes such as mild non‐proliferative diabetic retinopathy, moderate NPDR, and severe NPDR are accurately classified using the deep LSTM‐RFO algorithm. Experimentally, the MESSIDOR, STARE, and DRIVE datasets are used for both training and validation. MATLAB software performs the implementation process with respect to various evaluation criteria used. However, the proposed method accomplished superior performance, such as 98.45% specificity, 96.78% sensitivity, 97.92% precision, 96.89% recall, and 97.93% F‐score results in terms of DR classification than previous methods.
A novel method to ensure the security of the shared medical data using smart contracts: Organ transplantation sample
Authors: Çalık Elif , Kaya Hilal , Çelebi Fatih Vehbi
Published: December 2021

In recent years, the rapid development in information technologies appears in the form of digitalization, all of the processes in the health domain. Among the state‐of‐art, virtual reality, artificial intelligence, and blockchain technologies are among the most mentioned. In addition, the exponential increase in data kept in the electronic environment causes traditional central applications to face new challenges. The most important of these are accountability, transparency, security, cost, and time efficiency. In this study, a model based on blockchain technologies has been proposed to increase the transparency, accountability, and security of multi‐stakeholder shared medical data by using smart contracts (SCs). In the first part, there are briefly introduced the current situation of the health domain, blockchain technology, hyperledger fabric (HLF) and SCs. Afterward, in line with the latest technological developments, the studies carried out using the blockchain framework related to organ/tissue transplantation were examined. Lastly, the proposed framework was designed based on blockchain technologies for organ/tissue transplantation by using the HLF environment. The blockchain technology not only provides more visibility, more security, and better outcomes but also enables to store data securely and cheaply without allocating extra resources to a trusted authority. Thus, it can be ensured that the system is more transparent and more accountable.
A mass conserving arbitrary Lagrangian–Eulerian formulation for three‐dimensional multiphase fluid flows
Authors: Guventurk Cagatay , Sahin Mehmet
Published: December 2021

The arbitrary Lagrangian–Eulerian (ALE) framework presented in [Sahin and Guventurk, An arbitrary Lagrangian–Eulerian framework with exact mass conservation for the numerical simulation of 2D rising bubble problem.Int J Numer Methods Eng. 2017;112:2110–2134] has been extended to simulate three‐dimensional immiscible incompressible multiphase fluid flows. The div‐stable side centered unstructured finite volume formulation is used for the discretization of the incompressible Navier–Stokes equations. A novel kinematic boundary condition that satisfies the local discrete geometric conservation law (DGCL) is implemented to ensure the mass conservation of each species at the machine precision. The pressure field is treated to be discontinuous across the interface with the discontinuous treatment of density and viscosity. Surface tension force is treated as a tangent force and discretized in a semi‐implicit form. Two different approaches for the computation of unit normal vector have been implemented: the least squares biquadratic surface fitting (LSBSF) and the mean weighted by sine and edge length reciprocals (MWSELR). The resulting large system of algebraic equations is solved in a fully coupled manner in order to improve the time step restrictions. As a preconditioner, an approximate matrix factorization similar to that of the projection method is employed and the parallel algebraic multigrid solver BoomerAMG provided by the HYPRE library, which is accessed through the PETSc library, has been utilized for the scaled discrete Laplacian of pressure and the diagonal blocks of mesh deformation equations. The accuracy of the proposed method is initially validated on the static bubble problem, since the surface tension force is highly sensitive to the accurate evaluation of the unit normal vector and the inaccuracies significantly contribute to unphysical velocities, called parasitic currents. The calculations indicate that the parasitic currents can be reduced to machine precision for the MWSELR method. Then, the proposed approach is applied to the single bubble rising in a viscous quiescent liquid for both low and high density ratios. The calculations produce accurate predictions of the bubble shape, center of mass, rise velocity, and so forth. Furthermore, the mass of each species is conserved at machine precision and discontinuous pressure field is obtained in order to avoid errors due to the incompressibility restriction in the vicinity of liquid‐liquid interfaces at large density and viscosity ratios.
COVID‐19 prevention and control interventions: What can we learn from the pandemic management experience in Morocco?
Authors: Bouchriti Youssef , Kabbachi Belkacem , Sine Hasnaa , Naciri Aziz , Kharbach Ahmed , Baba Mohamed Amine , Achbani Abderrahmane
Published: December 2021

COVID‐19 is one of the worst outbreaks in infectious disease history. Through a succession of significant preventative and control interventions, Morocco has accumulated pandemic control experience. This study examines the available evidence on lessons learnt from the COVID‐19 pandemic management experience in Morocco. Social lockdown measures have helped restrain the exponential spread of new cases. These interventions appear to be reasonably successful. Their effectiveness must be confirmed by an assessment of other factors. This experience can help all countries develop effective pandemic prevention and control measures.
A human capital‐based framework of career, well‐being, and social information reasons for managerial lateral job assignment preferences
Authors: Campion Emily D. , Campion Michael A. , Campion Michael C.
Published: December 2021

Research on job assignments has generally assumed employees will accept assignments when offered. In this study, we examine managerial preferences for potential job assignment opportunities conceptualized using human capital theory to provide a holistic understanding of this phenomenon. Using two pilot studies, we refine the list of reasons managers use when forming lateral assignment preferences. In the main study, we collected data from a representative sample of more than 1200 managers in a large US organization who provided preferences for all possible assignment locations (about 40) in their regions and reported reasons for their preferences. Results showed career development reasons (e.g., promotion potential, opportunity to learn) and social information reasons (e.g., location manager, customers) attracted managers to assignments, and health and well‐being reasons (e.g., commuting, stress) repelled managers. There were several differences in these relationships by managerial level such that health and well‐being reasons were more important than career development reasons for lower‐level managers than higher‐level managers, who seemed to generate their preferences based more evenly on both types of reasons. We ask whether gender moderates the relationship between health and well‐being reasons and preferences and find little support. We also explore whether manager racioethnicity moderates the relationship between community racioethnicity and preferences and find a few differences. Most findings were replicated when predicting actual movement 2 years later. Results suggest managerial preferences should consistently be considered in job assignment research and that organizations should obtain and use preference data when making internal staffing decisions.
A nomogram model can predict the risk of venous thromboembolism in postoperative patients with gynecological malignancies
Authors: Jiang Xiao‐Xiang , Li Xiao‐Yan , Zhang Jun , Wang Xiao‐Xiao , Lin Chao‐Qin
Published: December 2021

Objective

To explore independent factors influencing the risk of lower extremity deep vein thrombosis during the postoperative period in patients with gynecological malignancies by constructing a predictive model.

Methods

In our study, we collected 573 patients with gynecological malignancies in the postoperative period between September 2016 and September 2020, who were divided into a modeling (n = 402) and verification group (n = 171) according to a ratio of 7:3. Univariate and multivariate regression analyses were used to determine independent factors influencing deep vein thrombosis (DVT). A nomogram model was created and a risk score was calculated.

Results

Multivariate regression analysis showed that the independent factors affecting DVT among these patients included age, hyperlipidemia, abnormal uterine bleeding, degree of anemia, D‐dimer, operation time, and intraoperative blood loss. By incorporating these factors into a nomogram, we determined that the C‐index and calibration curve of the two groups both showed that the model distinguishes and fits well. Further comparing between the high‐ and low‐risk groups, we found that the model has favorable predictive performance.

Conclusion

The predictive nomogram for the risk of DVT in patients with gynecological malignancies in the postoperative period demonstrated good calibration and recognition accuracy. Further independent research is necessary to verify our results.
Trading hardware with medium reservation to tackle scalability in low‐cost, single‐channel LoRa networks
Authors: Figueiredo Alexandre , Luís Miguel , Zúquete André
Published: December 2021

LoRa is actually one of the most popular LPWAN technologies for IoT applications, due to its low‐power and long‐range transmissions. A single low‐cost, single‐channel LoRa Gateway is able to cover a large number of End‐Devices spread over a wide area. Gateway diversity is traditionally used to reduce the impact of packet losses: adding more Gateways can increase both delivery ratio and goodput, even when using a pure‐ALOHA access policy. However, such solution can be cost‐expensive and the adoption of control‐based medium access strategies, without violating the duty‐cycle constraints, can be, in some situations, a better option. In this letter, we compare the effectiveness of Gateway diversity against a medium access protocol with channel reservation. We evaluate if and in which scenarios, relatively to delivery ratio and goodput, in a single communication channel, it is better to add more Gateways to the system (hardware) or adopt a reservation protocol (software) for tackling the scaling‐up of the number of End‐Devices.
The impact of a student pharmacist‐led inpatient medication counseling initiative on medication safety in kidney transplant recipients
Authors: Gonzales Haley M. , Li Jiaying , Orara Joshua , Patel Neha , Bartlett Felicia , Parks Sarah E. , Pilch Nicole A.
Published: December 2021

Introduction

Engaging student pharmacists as pharmacist extenders to facilitate medication education may represent a unique pathway for preventing medication safety issues and mitigating downstream consequences in the high‐risk kidney transplant (KTX) population. The aim of this study was to describe the implementation and impact of a student pharmacist‐led counseling initiative designed to promote patient and caregiver understanding of transplant medications.

Methods

This is a single‐center, retrospective quality improvement initiative comparing adult KTX recipients who received interventional student pharmacist‐led education vs a historical cohort. Data on clinical outcomes, including the incidence of medication errors (MEs), adverse drug events (ADEs), and readmissions, was extracted from the patient's electronic medical record. In the intervention cohort, attendee satisfaction was assessed based on responses obtained from surveys distributed to patients and caregivers on the day they attended the student pharmacist‐led class.

Results

A total of 311 KTX recipients were included in this analysis; 149 in the intervention cohort and 162 in the historical cohort. Patients in the intervention cohort experienced more MEs than those in the historical cohort (31 vs 11; P < .001). Rates of ADEs within the first 30 days post‐transplant were comparable across cohorts (56 vs 52; P = .406). No significant difference in readmissions at days 7, 14, and 30 was observed between groups. Attendee satisfaction was high across all survey response fields.

Conclusion

The results of this study demonstrate that KTX recipients who participated in student‐pharmacist led medication counseling had comparable rates of ADEs and readmissions to those who did not, but were more likely to experience MEs. Future research is needed to explore the role of structured medication counseling and the utility of student pharmacists in the clinical setting.
Classification of diterpenoid alkaloids from Aconitum kusnezoffii Reichb. by liquid chromatography‐tandem mass spectrometry‐based on molecular networking
Authors: Jiang Zhi‐bo , Guo Huan‐huan , Hu Yun‐qi , Zhou Le‐rui , Deng Chao‐fan , Nan Ze‐dong , Ma Xiao‐li , Wu Xiu‐li
Published: December 2021

Trace amounts of components in traditional Chinese medicine are considered pharmacological active substances used for treating many serious diseases. However, purifying all the trace substances and making clear their structures are not easy. In this context, high‐performance liquid chromatography coupled with quadrupole time‐of‐flight tandem mass spectrometry based molecular networking was applied to investigate the chemical constituents of the roots of Aconitum kusnezoffii Reichb., which led to the identification of 33 nodes in different groups (N1–N33). Based on the excremental fragmentation pathway of known diterpenoid alkaloids (1–9) and comparisons of characteristic ions and characteristic loss of analogs in literature, the structures of unknown ions were deduced. This work lays a foundation for the evaluation of the clinical basis and mechanism of traditional Chinese medicine from the aspects of chemistry. In this paper, the method speculation of unknown natural products by means of molecular network method is expected to be applied in the discovery and change law of relevant active components in clinical pharmacology and the change of complex systems caused by trace active compounds.
Efficacy and safety of laser‐assisted combination chemotherapy: A follow‐up study of treatment with 5‐fluorouracil and cisplatin for basal cell carcinoma
Authors: Fredman Gabriella , Wenande Emily , Hendel Kristoffer , Togsverd‐Bo Katrine , Haedersdal Merete
Published: December 2021

Background and Objectives

There is a growing need for effective topical treatments for basal cell carcinoma (BCC). By altering the skin barrier, ablative fractional lasers (AFLs) enhance cutaneous uptake of the synergistic chemotherapeutic agents, cisplatin, and 5‐fluorouracil (5‐FU). In our recently reported clinical trial, AFL‐assisted delivery of cisplatin and 5‐FU showed favorable short‐term clearance rates of 95% with good cosmetic results at 3 months. This follow‐up study assessed sustained tumor clearance, safety, and cosmesis in the same patient cohort, observed 6‐ and 12‐months posttreatment.

Materials and Methods

This follow‐up study assessed AFL‐assisted cisplatin and 5‐FU in low‐risk BCC. Among the 18/19 patients who achieved clinical tumor clearance in our 3‐months primary trial, all were included for a 6‐months follow‐up. At 12 months, 17/19 were included due to one 6‐month residual. During follow‐up visits, treated areas were evaluated for signs of recurrent tumour by clinical inspection and optical coherence tomography (OCT). Residual tumors were confirmed histologically. Cosmetic outcome was evaluated at both follow‐up visits by patients and physicians.

Results

Overall, complete tumor clearance was 89% (17/19) and 79% (15/19) at 6 and 12 months, respectively. Clearance rate for superficial BCCs (sBCCs) 1 year after treatment was 100% (6/6) and lower for nodular BCC (nBCC) at 69% (9/13). Among recurrent tumors, 67% (2/3) had received only a single treatment and all were of the nodular subtype, situated in the head and neck area. All histologically confirmed BCC recurrences were identified by OCT. Cosmetic outcomes were similarly rated “good” or “excellent” by patients and evaluators (p = 0.289 and p = 0.250). Treatment‐related local skin reactions were mild and tolerable, consisting of persisting erythema in two patients at the end of the study. Dyspigmentation was commonly observed at both follow‐up visits, while the appearance of scarring resolved in the majority of patients between 6 months (56%; 10/18) and 12 months (76%; 13/17).

Conclusion

AFL‐assisted cisplatin + 5‐FU in double sessions represents an acceptable and safe treatment strategy for low‐risk sBCC, while clearance rates following single treatment or for nBCC seem inferior. This intensified topical strategy may be best suited to cases of multiple lesions or in instances where surgical excision or extended courses of at‐home therapy is challenging.
Safety and efficacy of endovenous laser ablation (EVLA) using 1940 nm and radial emitting fiber: 3‐year results of a prospective, non‐randomized study and comparison with 1470 nm
Authors: Setia Abhay , Schmedt Claus‐Georg , Beisswenger Anna , Dikic Slobodan , Demhasaj Sahit , Setia Ocean , Schmitz‐Rixen Thomas , Sroka Ronald
Published: December 2021

Objectives

To evaluate the safety, efficacy and ≥36 months outcomes of endovenous laser ablation (EVLA) by means of 1940 nm laser with radial fiber for the treatment of truncal vein insufficiency and compare the results to a historical cohort, obtained via reviewing the literature.

Methods

This prospective, non‐randomized, single‐center clinical study included 139 consecutive patients with 177 incompetent great saphenous (GSV, n = 135) and short saphenous veins (SSV, n = 42). The maximum laser power (Pmax. 10 W) and pullback velocity were adjusted individually (Vmax = 1 mm/s). The laser fiber was placed at the junction to the deep vein under duplex monitoring. Simultaneous phlebectomies were performed on all the patients. Regular follow up with clinical and duplex ultrasound examination (DUS) were carried out postoperatively at 1 month (1 M), 6 months (6 M), 12 months (12 M), 24 months (24 M), 36 months, and after that (≥36 M). The results were compared with three cohorts (total 616 EVLA procedures with 1470 nm laser and radial fiber) from literature (criteria: >100 procedures, follow‐up of ≥2 years).

Results

The follow‐up rate was 100%, 91%, 73%, 48%, and 23% of the truncal veins at 1, 6, 12, 24, and ≥36 M, respectively. In comparison to the literature using 1470, a lower average linear endovenous energy density (LEED) (53 vs. 77–82 J/cm) resulted in 100% (6 M) and 96.5% (24 M) occlusion rates, reduced local ecchymosis (2.2% vs. 3.2%–18.7%) and reduced average postoperative pain levels (1.3 vs. 2.18). Regarding adverse events, induration (1.1% vs. 1.8%), skin burns (0% vs. 0.45%), endovenous heat‐induced thrombus propagation (EHIT) in the deep veins (2.3% vs. 1.8%) and laser‐induced persistent paresthesia (2.2% vs. 0.5%–2.9%) were comparable. Recanalizations observed in this study (GSV 0, SSV 3) were asymptomatic and required no treatment. At ≥36 M reflux in the accessory veins was observed in 5% versus 10.5% of patients. Reintervention was required in none (0% vs. 21%). At >36 M, short average stump lengths of 1 cm (GSV) and 0.3 cm (SSV) were observed.

Conclusion

EVLA with 1940 nm laser with radial emitting fiber is as safe and effective as 1470 nm laser for the treatment of truncal vein insufficiency. Lower postoperative pain, low analgesic requirements, short convalescence add to patients’ comfort. EVLA with 1940 nm laser‐guided by intraoperative DUS permits reproducible placement of the radial fiber at the saphenofemoral and saphenopopliteal junction, enabling further studies to assess the effect of shorter stump length on patterns and frequency of recurrence without increased risk of EHIT.
An extended finite element method with polygonal enrichment shape functions for crack propagation and stiff interfaceproblems
Authors: Latifaghili Amir , Bybordiani Milad , Erkmen Recep Emre , Dias‐da‐Costa Daniel
Published: December 2021

The extended/generalized finite element method has proven significant efficiency for handling crack propagation and internal boundaries. In certain conditions, however, one of the major drawbacks relates to the representation of unrealistic traction oscillations, particularly in stiff interfaces. To the authors' best knowledge, the few remedies found in the literature depend on the type of underlying finite element, which in some aspects limits general applications. Since one of the major sources of oscillations is created by couplings within standard shape functions for certain crack arrangements, it is herein proposed a novel approach based on enrichment Laplace shape functions directly adapted to the underlying geometry of split subdomains. By doing so, all sources of oscillations are effectively removed, while enriched degrees of freedom are defined exclusively on one side of the domain. The performance is studied using both element and structural examples with highly stiff cracks. More importantly, further assessment in more complex crack propagation problems, including mixed‐mode fracture of concrete beams and a peel test, shows excellent agreement with experimental/numerical data in terms of load‐displacement curves and traction profiles. Results are shown to be objective with respect to the mesh for stiffness values virtually representing infinitely stiff interfaces.
Cut points and sensitivity to change of the Enfranchisement scale of the Community Participation Indicators in adults with traumatic brain injury
Authors: Kersey Jessica , Baum Carolyn M. , Hammel Joy , Terhorst Lauren , McCue Michael , Skidmore Elizabeth R.
Published: December 2021

Background

Community participation is an important outcome of rehabilitation following traumatic brain injury. Yet, few measures assess inclusion and belonging (enfranchisement) as a dimension of community participation. The Enfranchisement scale of the Community Participation Indicators addresses this need. However, research on its psychometric properties is lacking.

Objective

To examine cut points and sensitivity to change of the Enfranchisement scale of the Community Participation Indicators in adults with traumatic brain injury.

Design

This was a repeated measures study with assessments administered twice (3 months apart).

Setting

Assessments were administered either over the phone, virtually (Zoom), or in person at the participant's home.

Participants

A total of 44 participants from community settings who had either experienced a traumatic brain injury within the previous year or were receiving rehabilitation interventions were recruited.

Main Outcome Measure

The Enfranchisement scale has two subscales: the Control subscale (range: 13‐65) and the Importance subscale (range: 14‐70). On both subscales, lower scores indicate better enfranchisement.

Methods

The software SAS PROC Logistic and the macro %ROCPlot were used to examine cut points at varying levels of sensitivity and specificity. The area under the receiver operating characteristics curve was calculated to determine overall classification accuracy. Minimum detectable change and minimal clinically important difference were also calculated.

Results

For the Control subscale, a cut point of 44 (area under the curve = .75), a minimum detectable change of 8, and a minimal clinically important difference of 5 were found. For the Importance subscale, a cut point of 39 (area under the curve = .81), a minimum detectable change of 8, and a minimal clinically important difference of 5 were found.

Conclusions

The cut points resulted in good classification accuracy, providing support for their reliability. The results provided evidence that both subscales are sensitive to change in adults with brain injury.
Structural and dynamic studies of the peptidase domain from Clostridium thermocellum PCAT1
Authors: Bhattacharya Shibani , Palillo Anthony
Published: December 2021

The export of antimicrobial peptides is mediated by diverse mechanisms in bacterial quorum sensing pathways. One such binary system employed by gram‐positive bacteria is the PCAT1 ABC transporter coupled to a cysteine protease. The focus of this study is the N‐terminal C39 peptidase (PEP) domain from Clostridium thermocellum PCAT1 that processes its natural substrate CtA by cleaving a conserved ‐GG‐ motif to separate the cargo from the leader peptide prior to secretion. In this study, we are primarily interested in elucidating the dynamic and structural determinants of CtA binding and how it is coupled to cleavage efficiency in the PCAT1 PEP domain. To this end, we have characterized CtA interactions with PEP domain and PCAT1 transporter in detergent micelles using solution nuclear magnetic resonance spectroscopy. The bound CtA structure revealed the disordered C‐terminal cargo peptide is linked by a sterically hindered cleavage site to a helix docked within a hydrophobic cavity in the PEP domain. The wide range of internal motions detected by amide nitrogen (N15) relaxation measurements in the free enzyme and substrate‐bound complex suggests the binding site is relatively floppy. This flexibility plays a key role in the structural rearrangement necessary to relax steric inhibition in the bound substrate. In conjunction with previously reported PCAT1 structures, we offer fresh insight into the ATP‐mediated association between PEP and transmembrane domains as a putative mechanism to optimize peptide cleavage by regulating the width and flexibility of the enzyme active site.
A newly introduced salt bridge cluster improves structural and biophysical properties of de novoTIM barrels
Authors: Kordes Sina , Romero‐Romero Sergio , Lutz Leonie , Höcker Birte
Published: December 2021

Protein stability can be fine‐tuned by modifying different structural features such as hydrogen‐bond networks, salt bridges, hydrophobic cores, or disulfide bridges. Among these, stabilization by salt bridges is a major challenge in protein design and engineering since their stabilizing effects show a high dependence on the structural environment in the protein, and therefore are difficult to predict and model. In this work, we explore the effects on structure and stability of an introduced salt bridge cluster in the context of three different de novo TIM barrels. The salt bridge variants exhibit similar thermostability in comparison with their parental designs but important differences in the conformational stability at 25°C can be observed such as a highly stabilizing effect for two of the proteins but a destabilizing effect to the third. Analysis of the formed geometries of the salt bridge cluster in the crystal structures show either highly ordered salt bridge clusters or only single salt bridges. Rosetta modeling of the salt bridge clusters results in a good prediction of the tendency on stability changes but not the geometries observed in the three‐dimensional structures. The results show that despite the similarities in protein fold, the salt bridge clusters differently influence the structural and stability properties of the de novo TIM barrel variants depending on the structural background where they are introduced.
Current situation and forecasting of resistance evolution to lambda‐cyhalothrin in Spanish medfly populations
Authors: Guillem‐Amat Ana , López‐Errasquín Elena , Castells‐Sierra Javier , Sánchez Lucas , Ortego Félix
Published: December 2021

BACKGROUND

The control of the Mediterranean fruit fly Ceratitis capitata (Wiedemann) in Spanish field populations mainly relies on the insecticides lambda‐cyhalothrin and spinosad as bait sprays. However, their sustainable used is compromised by the development of lambda‐cyhalothrin resistance and the detection of spinosad resistant alleles. In addition, the use of lure‐and‐kill traps covered with deltamethrin has increased in the last years. It is thus urgent to predict the impact that the combination of both pyrethroids will have in the evolution of lambda‐cyhalothrin resistance and how they could be combined with spinosad so as to establish proper resistance management programs.

RESULTS

Toxicity bioassays were performed to analyze the current levels of lambda‐cyhalothrin resistance in field populations, proving that it has remained stable in the last decade. An evolutionary model was established to explore the weight of selected parameters in the evolution of lambda‐cyhalothrin resistance in C. capitata and to forecast resistance development under different resistance management scenarios. Our results highlight the importance of fitness cost and inheritance to fit the experimental results. The analyses predicted that the rotation of lambda‐cyhalothrin and spinosad, when deltamethrin traps are also deployed in the field, will slow down the evolution of resistance, especially when cross‐resistance between both pyrethroids is considered.

CONCLUSION

Lambda‐cyhalothrin resistance has not increased in the last decade, probably due to the alternation of this insecticide with spinosad. Our modelling results indicate that the best option to avoid an increase in lambda‐cyhalothrin resistant alleles, considering that deltamethrin use is growing, would be to continue combining their use with spinosad. © 2021 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Nature's nitrite-to-ammonia expressway, with no stop at dinitrogen
Authors: Kroneck Peter M. H.
Published: December 2021

Since the characterization of cytochrome c552 as a multiheme nitrite reductase, research on this enzyme has gained major interest. Today, it is known as pentaheme cytochrome c nitrite reductase (NrfA). Part of the NH4+ produced from NO2− is released as NH3 leading to nitrogen loss, similar to denitrification which generates NO, N2O, and N2. NH4+ can also be used for assimilatory purposes, thus NrfA contributes to nitrogen retention. It catalyses the six-electron reduction of NO2− to NH4+, hosting four His/His ligated c-type hemes for electron transfer and one structurally differentiated active site heme. Catalysis occurs at the distal side of a Fe(III) heme c proximally coordinated by lysine of a unique CXXCK motif (Sulfurospirillum deleyianum, Wolinella succinogenes) or, presumably, by the canonical histidine in Campylobacter jejeuni. Replacement of Lys by His in NrfA of W. succinogenes led to a significant loss of enzyme activity. NrfA forms homodimers as shown by high resolution X-ray crystallography, and there exist at least two distinct electron transfer systems to the enzyme. In γ-proteobacteria (Escherichia coli) NrfA is linked to the menaquinol pool in the cytoplasmic membrane through a pentaheme electron carrier (NrfB), in δ- and ε-proteobacteria (S. deleyianum, W. succinogenes), the NrfA dimer interacts with a tetraheme cytochrome c (NrfH). Both form a membrane-associated respiratory complex on the extracellular side of the cytoplasmic membrane to optimize electron transfer efficiency. This minireview traces important steps in understanding the nature of pentaheme cytochrome c nitrite reductases, and discusses their structural and functional features.

Graphical abstract