bluuebunny/crossref_metadata_2025 huggingface dataset:
On the encoding capacity of human motor adaptation
Authors: Kim Seungyeon , Kwon Jaewoon , Kim Jin-Min , Park Frank Chongwoo , Yeo Sang-Hoon
Published: June 2021

We propose a novel concept called “encoding capacity” of motor adaptation, which describes an inherent limiting-factor of our brain’s ability to learn new motor skills, just like any other storage system. By reinterpreting the existing primitive-based models of motor learning, we hypothesize that the encoding capacity is determined by the size of the movement, and present a set of experimental evidence suggesting that such limiting effect of encoding capacity does exist in human motor adaptation.
Clinical Observation of Intraosseous Anesthesia in Percutaneous Kyphoplasty
Authors: Bao Li-Shuai , Wu Wei , Wang Xin , Zhong Xi-Hong , Wang Lin-Xiu , Wang Hong
Published: June 2021

Objective. Percutaneous kyphoplasty (PKP) is an effective minimally invasive technique in spine surgery in recent years. General anesthesia and local anesthesia are the main ways of anesthesia in PKP, and epidural anesthesia is also applied to PKP to some extent. However, all these three anesthetic methods have their respective advantages and disadvantages. It is essential to compare and evaluate the effects of different anesthesia methods on PKP for treating spinal fractures. Method. A total of 45 patients (53 vertebral bodies were included) were divided into two groups. Group A included 24 patients (29 vertebral bodies) with an average of 71 years old and Group B included 21 patients (24 vertebral bodies) with an average of 74 years old. Visual analogue scale (VAS) scores were recorded preoperatively; balloon expansion and bone cement injection were conducted intraoperatively. Then, they were recorded immediately after operation, 6 h postoperatively, to assess the pain level of the patient. Moreover, hospitalization time (days), operation duration (minutes), and bone cement injection amount (mL) had also been recorded. Results. There was no significant difference in preoperative general information and VAS score. However, the VAS scores were statistically significant at both the moment of balloon expansion and injection of bone cement. At the moment of immediate postoperation, the VAS scores showed no statistically significant difference, while it showed a statistically significant difference 6 h postoperatively. Conclusion. The anesthesia method by injection of 1% lidocaine hydrochloride (5 ml) into vertebral body can effectively relieve patients’ pain in intraoperation and postoperation.
Comparison and Analysis between the NAV6 Embolic Protection Filter and SpiderFX EPD Filter in Superficial Femoral Artery Lesions
Authors: Krishnan Prakash , Tarricone Arthur , Gee Allen , Farhan Serdar , Kamran Haroon , Kini Annapoorna , Sharma Samin
Published: June 2021

Objective. To compare the safety and efficacy between the SpiderFX EPD and Emboshield NAV6 filter in the collection of embolic debris created from lower limb atherectomy procedures in patients with PAD. Materials and Methods. Between January 2014 and October 2015, 507 patients with symptomatic peripheral artery disease were treated with directional atherectomy (SilverHawk), rotational atherectomy (JetStream), or laser atherectomy (Turbo Elite) based on operator discretion. Emboshield NAV6 (n = 161) and SpiderFX (n = 346) embolic protection devices were used with each of the 3 atherectomy devices. The primary study endpoint was 30-day freedom from major adverse events (MAEs). An MAE was defined as death, MI, TVR, thrombosis, dissection, distal embolization, perforation at the level of the filter, and unplanned amputation. A descriptive comparison of the MAE rates between Emboshield NAV6 and SpiderFX embolic protection devices was conducted. Results. The freedom from major adverse event (MAE) rate was 92.0% (CI: 86.7%, 95.7%) in patients who received an Emboshield NAV6 filter compared to 91.6% (CI: 88.2%, 94.3%) in patients who received the SpiderFX filter (

p
=
0.434

). The lower limit of 86.7% freedom from major adverse event rate in the Emboshield NAV6 group was above the performance goal of 83% (

p
<
0.0008

). Conclusions. There were no significant clinical outcome differences between Emboshield NAV6 and SpiderFX EPD filters in the treatment of lower extremities. This evaluation indicates the safety and efficacy to use either filter device to treat PAD patients with lower extremity lesions.
The Restorative Effect of Red Guava (Psidium guajava L.) Fruit Extract on Pulmonary Tissue of Rats (Rattus norvegicus) Exposed to Cigarette Smoke
Authors: Meles Dewa Ketut , Mustofa Imam , Wurlina Wurlina , Susilowati Suherni , Utama Suzanita , Suwasanti Niluh , Putri Desak Ketut Sekar Cempaka
Published: June 2021

Since the damage to alveolar tissue due to cigarette smoke exposure (CSE) is lipid peroxidation, antioxidant treatment is needed. The red guava (Psidium guajava L.) fruit contains antioxidants derived from quercetin, lycopene, and vitamin C. This study aimed to determine the effect of red guava fruit extract (RGFE) on the alveolar tissue of rats exposed to cigarette smoke. The 25 rats (Rattus norvegicus) were divided into five groups. The control and T0 groups were only administered placebo, while T1, T2, and T3 groups were orally administered RGFE of 18.9, 37.8, and 56.7 mg/kg body weight daily for 44 days. The CSE dose of 20 suctions daily was conducted on T0, T1, T2, and T3 groups on days 15–44. On day 45, all rats were sacrificed for serum collection and histopathological lung slides with eosin-nigrosin staining. The result showed that CSE caused an increase

p
<
0.05

in malondialdehyde (MDA) levels, cell death, apoptosis, and necrosis percentages, congestion and thickening of alveolar septum tissue, and reduction in the alveolar diameter and alveolar number. Administration of RGFE suppressed those effects, and the highest dose of RGFE (T3) restored

p
>
0.05

MDA levels, percentage of apoptotic and necrosis, alveolar septal thickening, and alveolar diameter. However, the percentages of cell death, alveolar congestion, and the alveolar number were still worse

p
<
0.05

than in normal rats. It could be concluded that RGFE has proved relief and restoration of the alveolar tissue of rats exposed to cigarette smoke.
A Multirate Sensor Information Fusion Strategy for Multitask Fault Diagnosis Based on Convolutional Neural Network
Authors: Ma Xiangkai , Wang Pei , Zhang Bozhou , Sun Ming
Published: June 2021

In complicated mechanical systems, fault diagnosis, especially regarding feature extraction from multiple sensors, remains a challenge. Most existing methods for feature extraction tend to assume that all sensors have uniform sampling rates. However, complex mechanical systems use multirate sensors. These methods use upsampling for data preprocessing to ensure that all signals at the same scale can cause certain time‐frequency features to vanish. To address these issues, this paper proposes a Multirate Sensor Information Fusion Strategy (MRSIFS) for multitask fault diagnosis. The proposed method is based on multidimensional convolution blocks incorporating multisource information fusion into the convolutional neural network (CNN) architecture. Features with different sampling rates from the raw signals are run through a multichannel parallel fault feature extraction framework for fault diagnosis. Additionally, time‐frequency analysis technology is used to reveal fault information in the association between time and frequency domains. The simulation platform’s experimental results show that the proposed multitask model achieves higher diagnosis accuracy than the existing methods. Furthermore, manual feature selection for each task becomes unnecessary in MRSIFS, which has the potential toward a general‐purpose framework.
Ten‐Year Clinical Outcomes of Biodegradable Versus Durable Polymer New‐Generation Drug‐Eluting Stent in Patients With Coronary Artery Disease With and Without Diabetes Mellitus
Authors: Lenz Tobias , Koch Tobias , Joner Michael , Xhepa Erion , Wiebe Jens , Coughlan J. J. , Aytekin Alp , Ibrahim Tareq , Fusaro Massimiliano , Cassese Salvatore , Laugwitz Karl‐Ludwig , Schunkert Heribert , Kastrati Adnan , Kufner Sebastian , Byrne Robert A. , Massberg Steffen , Birkmeier K. Anette , Schulz Stefanie , Pache Jürgen , Seyfarth Melchior , Mehilli Julinda , Schömig Albert , Hoppmann Petra
Published: June 2021

Background

Extended long‐term follow‐up data of new‐generation drug‐eluting stents in patients with diabetes mellitus is scant. The aim of this study is to assess the 10‐year clinical outcome of new‐generation biodegradable polymer‐based sirolimus‐eluting stents (Yukon Choice PC) versus permanent polymer‐based everolimus‐eluting stents (XIENCE) in patients with and without diabetes mellitus.

Methods and Results

In a prespecified subgroup analysis, outcomes of patients with or without diabetes mellitus treated with drug‐eluting stents were compared. The primary end point of this analysis was major adverse cardiac event, the composite of death, myocardial infarction, or target lesion revascularization. The analysis includes a total of 1951 patients (560 patients with and 1391 patients without diabetes mellitus) randomized to treatment with Yukon Choice PC (n=1299) or Xience (n=652). Regarding the primary end point, at 10 years patients with diabetes mellitus showed significantly higher major adverse cardiac event rates than patients without diabetes mellitus (
P
<0.001; hazard ratio [HR], 1.41; 95% CI, 1.22–1.63). There was no significant difference between patients treated with Yukon Choice PC versus Xience, neither in the subgroup of patients with (
P
=0.91; HR, 1.01; 95% CI, 0.79–1.30) nor without diabetes mellitus (
P
=0.50; HR, 0.94; 95% CI, 0.79–1.21). Rates of definite/probable stent thrombosis were 2.3% in patients with and 1.9% in patients without diabetes mellitus (HR, 1.27; 95% CI, 0.34–2.60;
P
=0.52), without significant differences between study devices.

Conclusions

The clinical outcome of patients with diabetes after percutaneous coronary intervention with different new‐generation drug‐eluting stents is considerably worse than that of patients without diabetes mellitus, with event rates constantly increasing out to 10 years.

Registration

URL:
https://clinicaltrials.gov
. Unique Identifier: NCT00598676.
Low‐Level Tragus Stimulation Modulates Atrial Alternans and Fibrillation Burden in Patients With Paroxysmal Atrial Fibrillation
Authors: Kulkarni Kanchan , Singh Jagmeet P. , Parks Kimberly A. , Katritsis Demosthenes G. , Stavrakis Stavros , Armoundas Antonis A.
Published: June 2021

Background

Low‐level tragus stimulation (LLTS) has been shown to significantly reduce atrial fibrillation (AF) burden in patients with paroxysmal AF. P‐wave alternans (PWA) is believed to be generated by the same substrate responsible for AF. Hence, PWA may serve as a marker in guiding LLTS therapy. We investigated the utility of PWA in guiding LLTS therapy in patients with AF.

Methods and Results

Twenty‐eight patients with AF were randomized to either active LLTS or sham (earlobe stimulation). LLTS was delivered through a transcutaneous electrical nerve stimulation device (pulse width 200 μs, frequency 20 Hz, amplitude 10–50 mA), for 1 hour daily over a 6‐month period. AF burden over 2‐week periods was assessed by noninvasive continuous ECG monitoring at baseline, 3 months, and 6 months. A 5‐minute control ECG for PWA analysis was recorded during all 3 follow‐up visits. Following the control ECG, an additional 5‐minute ECG was recorded during active LLTS in all patients. At baseline, acute LLTS led to a significant rise in PWA burden. However, active patients receiving chronic LLTS demonstrated a significant reduction in both PWA and AF burden after 6 months (
P
<0.05). Active patients who demonstrated an increase in PWA burden with acute LLTS showed a significant drop in AF burden after 6 months of chronic LLTS.

Conclusions

Chronic, intermittent LLTS resulted in lower PWA and AF burden than did sham control stimulation. Our results support the use of PWA as a potential marker for guiding LLTS treatment of paroxysmal AF.
Four new Bent-toed geckos (Cyrtodactylus Gray: Squamata: Gekkonidae) from northeast India
Authors: PURKAYASTHA JAYADITYA , LALREMSANGA HMAR TLAWMTE , BOHRA SANATH CHANDRA , BIAKZUALA LAL , DECEMSON H.T. , MUANSANGA LAL , VABEIRYUREILAI MATHIPI , CHAUHAN SURAJ , RATHEE YASHPAL SINGH
Published: June 2021

Based on morphology and ND2 gene sequences, four new species of Cyrtodactylus, two each from the Indian states of Meghalaya and Mizoram are described herein. The new species are a part of the Cyrtodactylus khasiensis group. The species from Meghalaya represent the lowland clade whereas the species from Mizoram represent the highland clade within the south of Brahmaputra clade of Indo-Burmese Cyrtodactylus. The two distinct populations from Meghalaya are sister to one another, differing from each by an uncorrected p-distance 0.065 and collectively are sister to Cyrtodactylus septentrionalis. The species from Mizoram differ from each other by an uncorrected p-distance of 0.085–0.121 and collectively are sister to Cyrtodactylus montanus.
Manganese (II) chloride leads to dopaminergic neurotoxicity by promoting mitophagy through BNIP3-mediated oxidative stress in SH-SY5Y cells
Authors: Huang Yanning , Wen Qiaolin , Huang Jinfeng , Luo Man , Xiao Yousheng , Mo Ruikang , Wang Jin
Published: June 2021

Background

Manganese overexposure can induce neurotoxicity, lead to manganism and result in clinical manifestations similar to those of parkinsonism. However, the underlying molecular mechanism is still unclear. This study demonstrated that MnCl2 induces mitophagy and leads to neurotoxicity by promoting BNIP3-mediated reactive oxygen species (ROS) generation.

Methods

Human neuroblastoma SH-SY5Y cells were used throughout our experiments. Cell viability was detected by cell proliferation/toxicity test kits. Mitochondrial membrane potential was measured by flow cytometry. ROS generation was detected using a microplate reader. Protein levels were evaluated by Western blot. Transmission electron microscopy was used to evaluate mitochondrial morphology. Co-immunoprecipitation was used to verify the interaction between BNIP3 and LC3.

Results

MnCl2 led to loss of mitochondrial membrane potential and apoptosis of SH-SY5Y cells by enhancing expression of BNIP3 and conversion of LC3-I to LC3-II. Moreover, MnCl2 reduced expression of the mitochondrial marker protein TOMM20 and promoted interaction between BNIP3 and LC3. The results also indicated that a decrease in BNIP3 expression reduced the mitochondrial membrane potential loss, attenuated apoptosis and reduced mitochondrial autophagosome formation in SH-SY5Y cells after MnCl2 treatment. Finally, we found that manganese-induced ROS generation could be reversed by the antioxidant N-acetyl cysteine (NAC) or silencing BNIP3 expression.

Conclusions

BNIP3 mediates MnCl2-induced mitophagy and neurotoxicity in dopaminergic SH-SY5Y cells through ROS. Thus, BNIP3 contributes to manganese-induced neurotoxicity by functioning as a mitophagy receptor protein.
Environmental fate and effects assessment of human pharmaceuticals: lessons learnt from regulatory data
Authors: Schwarz Simon , Gildemeister Daniela , Hein Arne , Schröder Patrick , Bachmann Jean
Published: June 2021

Human pharmaceuticals are extensively studied and assessed before marketing approval. Since 2006, this also includes an assessment of environmental risks. In the European Union, this is based on the guideline on the environmental risk assessment of medicinal products for human use (EMEA/CHMP/SWP/4447/00 corr 2), which is currently under revision. For Germany, the German Environment Agency (UBA) is tasked with the evaluation of environmental risks of human pharmaceuticals. Applicants seeking approval of medicinal products need to submit fate and effect data, in case predicted environmental concentrations (PECs) exceed 10 ng/L in surface waters, or the substance is of specific concern through its mode of action or physico-chemical characteristics.

Over the last decade, this regulatory work resulted in an internal agency database containing effect data on approximately 300 active pharmaceutical ingredients (APIs). A considerable part of this data is currently not publicly available due to property rights held by the respective applicants. The database was evaluated to draw conclusions on how the current assessment approach may be improved.

The evaluation of aquatic effect data shows considerable variation in ecotoxic effect concentrations, but supports the current use of 10 ng/L as PEC action limit. For endocrine-active substances and antibiotics, a clear sensitivity profile was observed, which allows a more targeted assessment in the future. The conclusions drawn from terrestrial effect data are less clear, as the database itself is biased because information is only available for substances with high sorption. Further adaptations of the terrestrial assessment strategy, including action triggers, appear necessary. Fate data show a high persistence of many APIs: approximately 43% of all APIs are classified as very persistent; 12% of these show DT50 values in a range where abiotic or biotic degradation is not expected.

Overall, the evaluation has shown that improvements of the current guideline are possible.
The reduced genome of a heritable symbiont from an ectoparasitic feather feeding louse
Authors: Alickovic Leila , Johnson Kevin P. , Boyd Bret M.
Published: June 2021

Background

Feather feeding lice are abundant and diverse ectoparasites that complete their entire life cycle on an avian host. The principal or sole source of nutrition for these lice is feathers. Feathers appear to lack four amino acids that the lice would require to complete development and reproduce. Several insect groups have acquired heritable and intracellular bacteria that can synthesize metabolites absent in an insect’s diet, allowing insects to feed exclusively on nutrient-poor resources. Multiple species of feather feeding lice have been shown to harbor heritable and intracellular bacteria. We expected that these bacteria augment the louse’s diet with amino acids and facilitated the evolution of these diverse and specialized parasites. Heritable symbionts of insects often have small genomes that contain a minimal set of genes needed to maintain essential cell functions and synthesize metabolites absent in the host insect’s diet. Therefore, we expected the genome of a bacterial endosymbiont in feather lice would be small, but encode pathways for biosynthesis of amino acids.

Results

We sequenced the genome of a bacterial symbiont from a feather feeding louse (Columbicola wolffhuegeli) that parasitizes the Pied Imperial Pigeon (Ducula bicolor) and used its genome to predict metabolism of amino acids based on the presence or absence of genes. We found that this bacterial symbiont has a small genome, similar to the genomes of heritable symbionts described in other insect groups. However, we failed to identify many of the genes that we expected would support metabolism of amino acids in the symbiont genome. We also evaluated other gene pathways and features of the highly reduced genome of this symbiotic bacterium.

Conclusions

Based on the data collected in this study, it does not appear that this bacterial symbiont can synthesize amino acids needed to complement the diet of a feather feeding louse. Our results raise additional questions about the biology of feather chewing lice and the roles of symbiotic bacteria in evolution of diverse avian parasites.
Increased expression of transient receptor potential channels and neurogenic factors associates with cough severity in a guinea pig model
Authors: Guan Mengyue , Ying Sun , Wang Yuguang
Published: June 2021

Background

Previous studies suggest that transient receptor potential (TRP) channels and neurogenic inflammation may be involved in idiopathic pulmonary fibrosis (IPF)-related high cough sensitivity, although the details of mechanism are largely unknown. Here, we aimed to further explore the potential mechanism involved in IPF-related high cough sensitivity to capsaicin challenge in a guinea pig model of pulmonary fibrosis induced by bleomycin.

Methods

Western blotting and real-time quantitative polymerase chain reaction (RT-qPCR) were employed to measure the expression of TRP channel subfamily A, member 1 (TRPA1) and TRP vanilloid 1 (TRPV1), which may be involved in the cough reflex pathway. Immunohistochemical analysis and RT-qPCR were used to detect the expression of neuropeptides substance P (SP), Neurokinin-1 receptor (NK1R), and calcitonin gene-related peptide (CGRP) in lung tissues. Concentrations of nerve growth factor (NGF), SP, neurokinin A (NKA), neurokinin B (NKB), and brain-derived neurotrophic factor (BDNF) in lung tissue homogenates were measured by ELISA.

Results

Cough sensitivity to capsaicin was significantly higher in the model group than that of the sham group. RT-qPCR and immunohistochemical analysis showed that the expression of TRPA1 and TRPV1 in the jugular ganglion and nodal ganglion, and SP, NK1R, and CGRP in lung tissue was significantly higher in the model group than the control group. In addition, expression of TRP and neurogenic factors was positively correlated with cough sensitivity of the experimental animals.

Conclusion

Up-regulated expression of TRPA1 and TRPV1 in the cough reflex pathway and neurogenic inflammation might contribute to the IPF-related high cough sensitivity in guinea pig model.
Sociodemographic differences in motives for food selection: results from the LoCard cross-sectional survey
Authors: Konttinen Hanna , Halmesvaara Otto , Fogelholm Mikael , Saarijärvi Hannu , Nevalainen Jaakko , Erkkola Maijaliisa
Published: June 2021

Background

Although sociodemographic differences in dietary intake have been widely studied, the up-to-date evidence on the corresponding variations in motives for food selection is limited. We investigated how sociodemographic characteristics and special diets in households are associated with the relative importance of various food motives.

Methods

Participants were members of the S Group loyalty card program across Finland who consented to release their grocery purchase data to be used for research purposes and responded to a web-based questionnaire in 2018 (LoCard study). Self-reported information on sociodemographic factors (age, gender, marital status, living situation, education, household income), special diets in household and food motives (Food Choice Questionnaire) were utilized in the present analyses (N = 10,795). Age- and gender-adjusted linear models were performed separately for each sociodemographic predictor and motive dimension (derived by factor analysis) outcome. The importance of each sociodemographic predictor was evaluated based on an increase in R2 value after adding the predictor to the age- and gender-adjusted model.

Results

Age emerged as a central determinant of food motives with the following strongest associations: young adults emphasized convenience (∆R2 = 0.09, P < 0.001) and mood control (∆R2 = 0.05, P < 0.001) motives more than middle-aged and older adults. The relative importance of cheapness decreased with increasing socioeconomic position (SEP) (∆R2 = 0.08, P < 0.001 for income and ∆R2 = 0.04, P < 0.001 for education). However, the price item (“is good value for money”) depicting the concept of worth did not distinguish between SEP categories. Considerations related to familiarity of food were more salient to men (∆R2 = 0.02, P < 0.001) and those with lower SEP (∆R2 = 0.03, P < 0.001 for education and ∆R2 = 0.01, P < 0.001 for income). Respondents living in households with a vegetarian, red-meat-free, gluten-free or other type of special diet rated ethical concern as relatively more important than households with no special diets (∆R2 = 0.02, P < 0.001).

Conclusions

We observed sociodemographic differences in a range of food motives that might act as barriers or drivers for adopting diets that benefit human and planetary health. Interventions aiming to narrow SEP and gender disparities in dietary intake should employ strategies that take into account higher priority of familiarity and price in daily food selection in lower-SEP individuals and males.
Clinical validation of kinematic assessments of post-stroke upper limb movements with a multi-joint arm exoskeleton
Authors: Grimm Florian , Kraugmann Jelena , Naros Georgios , Gharabaghi Alireza
Published: June 2021

Background

The clinical evaluation of the upper limb of severely impaired stroke patient is challenging. Sensor-based assessments may allow for an objective evaluation of this patient population. This study investigated the validity of a device-assisted approach in comparison to the clinical outcome that it is supposed to reflect.

Methods

In nineteen severely impaired chronic stroke patients, we applied a gravity-compensating, multi-joint arm exoskeleton (Armeo Spring) and compared this sensor-based assessment with the clinical outcome measure Upper Extremity Fugl-Meyer Assessment (UE-FMA) scale. Specifically, we assessed separately and subsequently the range of motion in joint space for four single joints (i.e., wrist, elbow and shoulder flexion/extension (FE), and shoulder internal/external rotation (IER)), and the closing and opening of the hand with a pressure sensor placed in the handle.

Results

Within the kinematic parameters, a strong correlation was observed between wrist and elbow FE (r > 0.7, p < 0.003; Bonferroni corrected). The UE-FMA was significantly predicted by a multiple regression model (F (5, 13) = 12.22, p < 0.0005, adj.R2 = 0.83). Both shoulder IER and grip pressure added significantly (p < 0.05) to the prediction with the standardized coefficients β of 0.55 and 0.38, respectively.

Conclusions

By applying an exoskeleton-based self-contained evaluation of single-joint movements, a clinically valid assessment of the upper limb range of motion in severely impaired stroke patients is feasible. Shoulder IER contributed most relevantly to the prediction of the clinical status. These findings need to be confirmed in a large, independent patient cohort.
SARS-CoV-2 in hospital indoor environments is predominantly non-infectious
Authors: Krambrich Janina , Akaberi Dario , Ling Jiaxin , Hoffman Tove , Svensson Lennart , Hagbom Marie , Lundkvist Åke
Published: June 2021

Background

The ongoing SARS-CoV-2 pandemic has spread rapidly worldwide and disease prevention is more important than ever. In the absence of a vaccine, knowledge of the transmission routes and risk areas of infection remain the most important existing tools to prevent further spread.

Methods

Here we investigated the presence of the SARS-CoV-2 virus in the hospital environment at the Uppsala University Hospital Infectious Disease ward by RT-qPCR and determined the infectivity of the detected virus in vitro on Vero E6 cells.

Results

SARS-CoV-2 RNA was detected in several areas, although attempts to infect Vero E6 cells with positive samples were unsuccessful. However, RNase A treatment of positive samples prior to RNA extraction did not degrade viral RNA, indicating the presence of SARS-CoV-2 nucleocapsids or complete virus particles protecting the RNA as opposed to free viral RNA.

Conclusion

Our results show that even in places where a moderate concentration (Ct values between 30 and 38) of SARS-CoV-2 RNA was found; no infectious virus could be detected. This suggests that the SARS-CoV-2 virus in the hospital environment subsides in two states; as infectious and as non-infectious. Future work should investigate the reasons for the non-infectivity of SARS-CoV-2 virions.
EUS-guided drainage using lumen apposing metal stent and percutaneous endoscopic necrosectomy as dual approach for the management of complex walled-off necrosis: a case report and a review of the literature
Authors: Binda Cecilia , Sbrancia Monica , La Marca Marina , Colussi Dora , Vizzuso Antonio , Tomasoni Matteo , Agnoletti Vanni , Giampalma Emanuela , Ansaloni Luca , Fabbri Carlo
Published: June 2021

Background

Endoscopic ultrasound-guided drainage is suggested as the first approach in the management of symptomatic and complex walled-off pancreatic necrosis. Dual approach with percutaneous drainage could be the best choice when the necrosis is deep extended till the pelvic paracolic gutter; however, the available catheter could not be large enough to drain solid necrosis neither to perform necrosectomy, entailing a higher need for surgery. Therefore, percutaneous endoscopic necrosectomy through a large bore percutaneous self-expandable metal stent has been proposed.

Case presentation

In this study, we present the case of a 61-year-old man admitted to our hospital with a history of sepsis and persistent multiorgan failure secondary to walled-off pancreatic necrosis due to acute necrotizing pancreatitis. Firstly, the patient underwent transgastric endoscopic ultrasound-guided drainage using a lumen-apposing metal stent and three sessions of direct endoscopic necrosectomy. Because of recurrence of multiorgan failure and the presence of the necrosis deeper to the pelvic paracolic gutter at computed tomography scan, we decided to perform percutaneous endoscopic necrosectomy using an esophageal self-expandable metal stent. After four sessions of necrosectomy, the collection was resolved without complications. Therefore, we perform a revision of the literature, in order to provide the state-of-art on this technique. The available data are, to date, derived by case reports and case series, which showed high rates both of technical and clinical success. However, a not negligible rate of adverse events has been reported, mainly represented by fistulas and abdominal pain.

Conclusion

Dual approach, using lumen apposing metal stent and percutaneous self-expandable metal stent, is a compelling option of treatment for patients affected by symptomatic, complex walled-off pancreatic necrosis, allowing to directly remove large amounts of necrosis avoiding surgery. Percutaneous endoscopic necrosectomy seems a promising technique that could be part of the step-up-approach, before emergency surgery. However, to date, it should be reserved in referral centers, where a multidisciplinary team is disposable.
The short-term effectiveness and safety of second-generation patellofemoral arthroplasty and total knee arthroplasty on isolated patellofemoral osteoarthritis: a systematic review and meta-analysis
Authors: Li Chengxin , Li Zhizhuo , Shi Lijun , Gao Fuqiang , Sun Wei
Published: June 2021

Background

We aimed to compare second-generation patellofemoral arthroplasty (2G PFA) with total knee arthroplasty (TKA) in treating isolated patellofemoral osteoarthritis (PFOA) by assessing the percentages of revisions, complications, and patient-reported outcome measures (PROMs).

Methods

Studies that compared the outcomes of 2G PFA and TKA in the treatment of isolated PFOA were searched in electronic databases, including MEDLINE, Embase, and Web of Science. Two researchers independently identified eligible studies, extracted the data, and evaluated the quality of the literature. Pooled risk ratios (RRs) or weighted mean differences with 95% confidence intervals were calculated using either fixed or random effects models. Descriptive analysis was used when data could not be pooled.

Results

A total of six studies were included in the review. For the revision percentage and complications, there were no significant differences between 2G PFA and TKA (RR = 2.29, 95% CI 0.69–7.58, P = 0.17; RR = 0.56, 95% CI 0.23–1.40, P = 0.22, respectively). Second, the results demonstrated that the differences in the Oxford Knee Score (OKS) and the University of California, Los Angeles (UCLA) activity score between 2G PFA and TKA were not significant (WMD −4.68, 95% CI −16.32 to 6.97, p = 0.43; WMD 0.16, 95% CI −1.21 to 1.53, P = 0.82). The Knee Injury and Osteoarthritis Outcome Score (KOOS), the American Knee Society Score (AKSS), and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were presented in a narrative form due to methodological heterogeneity.

Conclusion

For isolated PFOA, 2G PFA demonstrated similar results to TKA with respect to the percentages of revisions, complications, and PROMs.
Atypical COVID-19 dynamics in a patient with mantle cell lymphoma exposed to rituximab
Authors: Marcacci Gianpaolo , Fiorentino Giuseppe , Volzone Francesco , Falcone Umberto , Parrella Roberto , Donnarumma Daniela , D’Ovidio Silvia , Annunziata Anna , Micallo Giovanni , Portella Giuseppe , De Chiara Annarosaria , De Filippi Rosaria , Crisci Stefania , Pinto Antonio
Published: June 2021

Patients with non-hodgkin lymphomas (NHL) represent a population of special interest during the current Coronavirus disease-19 (COVID-19) pandemics. NHLs are associated with disease- and treatment-related immunodeficiencies which may generate unusual COVID-19 dynamics and pose unique management challenges. We report the unusual clinical course of COVID-19 in a patient with mantle cell lymphoma (MCL) exposed to nine doses of Rituximab shortly before infection with severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). He had a prolonged asymptomatic phase, with negative molecular and antibody testing for SARS-CoV-2, followed by a rapidly progressive evolution to severe COVID-19. Despite detection of viral RNA overlapped with first symptoms occurrence, anti-SARS-CoV-2 antibodies displayed an asynchronous pattern, with IgG first appearing 2 days after RNA positivity and IgM never being detected throughout the entire clinical course. While disease-associated immune derangements and/or previous treatments involving anti-CD20 antibodies might have contributed to COVID-19 dynamics in our patient, data suggests that antibody testings, without concurrent molecular assessment for SARS-CoV-2, may turn inadequate for monitoring of MCL patients, and in general NHL patients heavily exposed to anti-CD20 antibodies, during the current pandemics. We suggest that repeated molecular testing of nasopharyngeal swab should be implemented in these subjects despite a negative serology and absence of symptoms of SARS-CoV-2 infection. For the same reasons, a customized strategy needs to be developed for patients exposed to anti-CD20 antibodies, based on different features and mechanism of action of available SARS-CoV-2 vaccines and novel vaccinomics developments.
An update on the distribution of Glossina (tsetse flies) at the wildlife-human-livestock interface of Akagera National Park, Rwanda
Authors: Gashururu Richard S. , Githigia Samuel M. , Gasana Methode N. , Habimana Richard , Maingi Ndichu , Cecchi Giuliano , Paone Massimo , Zhao Weining , Masiga Daniel K. , Gashumba James
Published: June 2021

Background

Glossina (tsetse flies) biologically transmit trypanosomes that infect both humans and animals. Knowledge of their distribution patterns is a key element to better understand the transmission dynamics of trypanosomosis. Tsetse distribution in Rwanda has not been well enough documented, and little is known on their current distribution. This study determined the current spatial distribution, abundance, diversity, and seasonal variations of tsetse flies in and around the Akagera National Park.

Methods

A longitudinal stratified sampling following the seasons was used. Biconical traps were deployed in 55 sites for 6 consecutive days of each study month from May 2018 to June 2019 and emptied every 48 h. Flies were identified using FAO keys, and the number of flies per trap day (FTD) was used to determine the apparent density. Pearson chi-square (χ2) and parametrical tests (t-test and ANOVA) were used to determine the variations between the variables. The significance (p < 0.05) at 95% confidence interval was considered. Logistic regression was used to determine the association between tsetse occurrence and the associated predictors.

Results

A total of 39,516 tsetse flies were collected, of which 73.4 and 26.6% were from inside Akagera NP and the interface area, respectively. Female flies accounted for 61.3 while 38.7% were males. Two species were identified, i.e. G. pallidipes [n = 29,121, 7.4 flies/trap/day (FTD)] and G. morsitans centralis (n = 10,395; 2.6 FTD). The statistical difference in numbers was significant between the two species (p = 0.000). The flies were more abundant during the wet season (15.8 FTD) than the dry season (4.2 FTD). Large numbers of flies were trapped around the swamp areas (69.1 FTD) inside the park and in Nyagatare District (11.2 FTD) at the interface. Glossina morsitans was 0.218 times less likely to occur outside the park. The chance of co-existing between the two species reduced outside the protected area (0.021 times).

Conclusions

The occurrence of Glossina seems to be limited to the protected Akagera NP and a narrow band of its surrounding areas. This finding will be crucial to design appropriate control strategies. Glossina pallidipes was found in higher numbers and therefore is conceivably the most important vector of trypanosomosis. Regional coordinated control and regular monitoring of Glossina distribution are recommended.

Graphical Abstract
Laparoscopic ileo-transverse bypass may contribute to achieving curative resection for locally advanced right colon cancer: a case report
Authors: Tabe Shunsuke , Tonooka Toru , Hoshino Isamu , Takiguchi Nobuhiro , Soda Hiroaki , Gunji Hisashi , Nabeya Yoshihiro , Ohtsuka Masayuki
Published: June 2021

Background

The strategy for treating obstructive colon cancers with metastatic lesions remains unclear. Herein, we report a case of laparoscopic ileo-transverse colon bypass (LITB) before preoperative chemotherapy for an obstructive right colon cancer.

Case presentation

A 59-year-old woman was referred to our institution (Department of Gastroenterological Surgery, Chiba Cancer Center) for liver tumors detected on ultrasound. The clinical diagnosis was ascending colon cancer with multiple liver metastases. Based on the criteria of the International Union against Cancer Committee, 8th edition, the staging was confirmed as cT4aN1M1a(H), cStage IV. Although the primary tumor in the ascending colon extended beyond the colonic wall, curative resection was possible for both primary and metastatic tumors. We planned to administer chemotherapy before the radical surgery to obtain tumor-free resection margins; however, as the obstruction was fatal, LITB was prioritized and performed using five ports. An intracorporeal side-to-side anastomosis was performed between the ileum, 25 cm from the terminal ileum, and the transverse colon. The patient was discharged on postoperative day 18 without any complications. After LITB, for preoperative chemotherapy, five courses of capecitabine plus oxaliplatin (CapeOX) + bevacizumab were administered. Six weeks after the preoperative chemotherapy, right hemicolectomy with D3 lymph node dissection and right hepatectomy were performed. Pathological findings of the resected specimen confirmed curative resection of both lesions, and a favorable effect of chemotherapy was obtained. The patient has been alive for over 8 months after the surgery, with no evidence of cancer recurrence.

Conclusions

This case report demonstrates the effectiveness of LITB for obstructive right colon cancer in patients who need preoperative chemotherapy.
Investigating the binding affinity, molecular dynamics, and ADMET properties of 2,3-dihydrobenzofuran derivatives as an inhibitor of fungi, bacteria, and virus protein
Authors: Nath Ashutosh , Kumer Ajoy , Zaben Fahmida , Khan Md. Wahab
Published: June 2021

Background

2,3-Dihydrobenzofurans (DHB) have proposed as advantages structures, and used as chemical entresol to design small compound libraries. The present study illustrates to explore 2,3-dihydrobenzofurans(DHB) in comparison to selected some derivatives drugs by using molecular docking and molecular dynamics, as well as ADMET studies. The online database “Molinspiration online server” was used to detect the physicochemical pharmacokinetics and drug likeness score of DHB drugs. For estimation of molecular docking, six pathogens, such as Aspergillus niger (PDB id: 1kum), Candida albicans (3dra), Escherichia coli (6og7), Salmonella typhi (4k6l), Influenza (1ru7), and Hepatitis C (4tyd), were chosen due to close biological studies.

Results

From Molinspiration online server has showed that DHB did not violate the “Lipinski five rule” as drugs, leading compound for molecular docking exhibited the potential interaction to the active residue. The binding affinity of DHB2 (−7.00 kcal/mol) against 3dra was higher than DHB8 (−6.40 kcal/mol) and DHB (5.70 kcal/mol) for compounds. The results of molecular docking show that the compounds mentioned in this study are not equally effective against pathogens, such as fungi, viruses, and bacteria. However, DHB2, DHB3, and DHB 8 compounds can work against almost given pathogens which results are derived from auto dock vina in terms of binding affinity around 6.00 kcal/mol, and Fire Dock has values from about 38.0 to 42.0 kcal/mol. To explore the dynamic nature of the interaction, 50 ns molecular dynamics (MD) simulation was performed on the selected protein-DHB complexes. Thus, DHB 8 has greater potential to interact for further for fungi.

Conclusion

Finding from this study can play an effective role as a drug in any biological system. This study as well recommends to researchers to synthesize these DHBs for evaluation of its biological activity.

Graphical abstract
Forecasting asparaginase quantity required to treat pediatric ALL in LMICs using ACCESS FORxECAST.
Authors: Hughes Terence M. , Empringham Brianna , Gupta Sumit , Ward Zachary J. , Yeh Jennifer , Wagner Anita K. , Silverman Lewis B. , Frazier Lindsay Lindsay , Denburg Avram
Published: June 2021

10031

Background: Asparaginase (ASN) is a crucial component of pediatric acute lymphoblastic leukemia (ALL) protocols. ASN is available in three enzyme formulations: native from Escherichia Coli ( E. coli), PEGylated from E. coli (PEG), and native erwinia from Erwinia chrysanthemi (Erwinase). PEG is typically preferred in high-income countries, while E. coli is more accessible in low and middle income countries (LMICs). Erwinase is reserved for patients who develop hypersensitivity. Short shelf lives, high prices, intermittent availability, and concern for substandard formulations in LMICs have created a need for proactive ASN demand estimates, particularly in LMICs. Methods: We modified FORxECAST, a publicly available tool that forecasts pediatric cancer drug quantity and cost, to estimate ASN quantity required to treat pediatric ALL in 2021 across all LMICs. Incidence data is based on the Global Childhood Cancer microsimulation model, which extrapolates country registries to estimate diagnosed pediatric ALL patients. We forecast ASN quantity for both a base regimen (BR), recommended by the International Pediatric Oncology Society (SIOP), and a more aggressive regimen (AR) used in some LMICs with more advanced supportive care capacity. For both BR and AR, we estimate ASN quantity across four scenarios, outlining how quantity would vary based on formulation and ability to switch in cases of hypersensitivity. Results: The estimated quantity of ASN required to treat all children diagnosed with ALL in LMICs in 2021, across scenarios and regimens, is provided (Table). If E. coli were used to treat all diagnosed pediatric ALL patients across LMICs, required quantity would range from 1,198 M IU (BR) to 1,661 M IU (AR) (Scenario 1). If PEG were used, required quantity would range 150 M IU (BR) to 473 M IU (AR) (Scenario 2). Accounting for hypersensitivity would require 77 M IU (BR) to 137 M IU (AR) Erwinase (Scenarios 3 and 4). Conclusions: We adapted FORxECAST to be ASN-specific and estimated demand in LMICs for a range of scenarios, including for second line Erwinase; accounting for hypersensitivity is particularly important because discontinuation typically results in lower cure rates. We also estimated how quantity of ASN required would increase with treatment intensity. These results provide the first quantification of ASN need for pediatric ALL in LMICs, creating a demand estimate that can inform private and public efforts to produce a reliable supply of high quality ASN for all children with ALL.[Table: see text]
The landscape of germline mutations and the relationship with tumor mutation burden in Chinese patients with lung cancer.
Authors: Shi Jian , Liu Rongfeng , Huang Guanglei , Wang Lixing , Shan Baoen , Luo Ningning , Zhang Qin , Guo Didi , Wu Yaqing , Qi Yingxue
Published: June 2021

10522

Background: Lung cancer is one of the most common types of cancer, ranking the first in the incidence and mortality of malignant tumors in the world and China. Although studies have been reported that genetic susceptibility to lung cancer is associated with certain germline mutations, the relationship between lung cancer risk and inherited genetic factors remains relatively elusive. However, the effect of germline mutation on TMB in lung cancer has not been explored. Herein, DNA genomic profiling was performed through NGS with a 539-gene panel to explore the germline mutations and the relationship with TMB in Chinese patients with lung cancer. Methods: We retrospectively analyzed the germline mutations through a comprehensive 539-gene profiling of 3541 Chinese patients with lung cancer. 539-gene panel contained germline mutations in 90 hereditary tumor-associated genes. We screened out the pathogenic and likely pathogenic germline mutations according to the standards and guidelines for the interpretation of sequence variants of The American College of Medical Genetics and Genomics (ACMG), and picked out there is no records in Clinvar database and no literature report. TMB of tissue or blood ctDNA in 3541 patients were further analyzed in with pathogenic mutations (P group), with likely pathogenic mutations (LP group), and no germline mutations group (Non-P group). The difference in TMB was analyzed via the Wilcoxon sign test. Results: In 3541 patients with lung cancer, 177 (4.999%) patients were identified harboring pathogenic or likely pathogenic germline mutations, in which 78 P group and 99 LP group, the rest 3364 were Non-P group. The highest prevalence of germline mutation was found in BRCA2 (0.565%), ATM (0.339%), MUTYH (0.282%), and BRCA1 (0.254%). In 177 patients with pathogenic or likely pathogenic germline mutations, 67 mutations were recorded as UNK (unknow) in Clinvar database and no literature report. The media TMB of tissue in P group, LP group and Non-P group were 5.149, 5.535 and 5.547 respectively. The media TMB of blood ctDNA in P group, LP group and Non-P group were 4.257, 3.945 and 4.483 respectively. There was no statistical difference in TMB between P and Non-P groups (tissue p = 0.98; ctDNA p = 0.5). Conclusions: In our study, we firstly identified 67 novel germline mutations and studied on the relationship between germline mutations and TMB in lung cancer, which expanded the understanding of germline mutations.