bluuebunny/crossref_metadata_2025 huggingface dataset:
Oscillating calcium signals in smooth muscle cells underlie the persistent basal tone of internal anal sphincter
Authors: Lu Ping , Chen Jun , Zhang Chenghai , Saur Dieter , Baer Christina E. , Lifshitz Lawrence M. , Fogarty Kevin E. , ZhuGe Ronghua
Published: January 2021

A persistent basal tone in the internal anal sphincter (IAS) is essential for keeping the anal canal closed and fecal continence; its inhibition via the rectoanal inhibitory reflex (RAIR) is required for successful defecation. However, cellular signals underlying the IAS basal tone remain enigmatic. Here we report the origin and molecular mechanisms of calcium signals that control the IAS basal tone, using a combination approach including a novel IAS slice preparation that retains cell arrangement and architecture as in vivo, 2‐photon imaging, and cell‐specific gene‐modified mice. We found that IAS smooth muscle cells generate two forms of contractions (i.e., phasic and sustained contraction) and Ca2+ signals (i.e., synchronized Ca2+ oscillations [SCaOs] and asynchronized Ca2+ oscillations [ACaOs]) that last for hours. RyRs, TMEM16A, L‐type Ca2+ channels, and gap junctions are required for SCaOs, which account for phasic contraction and 75% of sustained contraction. Nevertheless, only RyRs are required for ACaOs, which contribute 25% of sustained contraction. Nitric oxide, the primary neurotransmitter mediating the RAIR, blocks both types of Ca2+ signals, leading to IAS's full relaxation. Our results show that the oscillating nature of Ca2+ signals generates and maintains the basal tone without causing cytotoxicity to IAS. Our study provides insight into fecal continence and normal defecation.
Impact of prolonged sepsis on neural and muscular components of muscle contractions in a mouse model
Authors: Goossens Chloë , Weckx Ruben , Derde Sarah , Van Helleputte Lawrence , Schneidereit Dominik , Haug Michael , Reischl Barbara , Friedrich Oliver , Van Den Bosch Ludo , Van den Berghe Greet , Langouche Lies
Published: January 2021

Background

Prolonged critically ill patients frequently develop debilitating muscle weakness that can affect both peripheral nerves and skeletal muscle. In‐depth knowledge on the temporal contribution of neural and muscular components to muscle weakness is currently incomplete.

Methods

We used a fluid‐resuscitated, antibiotic‐treated, parenterally fed murine model of prolonged (5 days) sepsis‐induced muscle weakness (caecal ligation and puncture; n = 148). Electromyography (EMG) measurements were performed in two nerve–muscle complexes, combined with histological analysis of neuromuscular junction denervation, axonal degeneration, and demyelination. In situ muscle force measurements distinguished neural from muscular contribution to reduced muscle force generation. In myofibres, imaging and biomechanics were combined to evaluate myofibrillar contractile calcium sensitivity, sarcomere organization, and fibre structural properties. Myosin and actin protein content and titin gene expression were measured on the whole muscle.

Results

Five days of sepsis resulted in increased EMG latency (P = 0.006) and decreased EMG amplitude (P < 0.0001) in the dorsal caudal tail nerve–tail complex, whereas only EMG amplitude was affected in the sciatic nerve–gastrocnemius muscle complex (P < 0.0001). Myelin sheath abnormalities (P = 0.2), axonal degeneration (number of axons; P = 0.4), and neuromuscular junction denervation (P = 0.09) were largely absent in response to sepsis, but signs of axonal swelling [higher axon area (P < 0.0001) and g‐ratio (P = 0.03)] were observed. A reduction in maximal muscle force was present after indirect nerve stimulation (P = 0.007) and after direct muscle stimulation (P = 0.03). The degree of force reduction was similar with both stimulations (P = 0.2), identifying skeletal muscle, but not peripheral nerves, as the main contributor to muscle weakness. Myofibrillar calcium sensitivity of the contractile apparatus was unaffected by sepsis (P ≥ 0.6), whereas septic myofibres displayed disorganized sarcomeres (P < 0.0001) and altered myofibre axial elasticity (P < 0.0001). Septic myofibres suffered from increased rupturing in a passive stretching protocol (25% more than control myofibres; P = 0.04), which was associated with impaired myofibre active force generation (P = 0.04), linking altered myofibre integrity to function. Sepsis also caused a reduction in muscle titin gene expression (P = 0.04) and myosin and actin protein content (P = 0.05), but not the myosin‐to‐actin ratio (P = 0.7).

Conclusions

Prolonged sepsis‐induced muscle weakness may predominantly be related to a disruption in myofibrillar cytoarchitectural structure, rather than to neural abnormalities.
Incidental intrahepatic cholangiocarcinoma in patients undergoing liver transplantation: A multi‐center study in Japan
Authors: Hara Takanobu , Eguchi Susumu , Yoshizumi Tomoharu , Akamatsu Nobuhisa , Kaido Toshimi , Hamada Takashi , Takamura Hiroyuki , Shimamura Tsuyoshi , Umeda Yuzo , Shinoda Masahiro , Ogura Yasuhiro , Fukumoto Takumi , Kasahara Mureo , Hibi Taizo , Umeshita Koji , Furukawa Hiroyuki , Ohdan Hideki
Published: January 2021

Background

Intrahepatic cholangiocarcinoma had been considered a contraindication for liver transplantation because of poorer outcomes. However, incidental intrahepatic cholangiocarcinoma in the explanted liver has been reported because of the difficulty of obtaining an accurate diagnosis in cirrhotic livers on preoperative imaging.

Methods

We conducted a nationwide survey to analyze the incidence of incidental intrahepatic cholangiocarcinoma and outcomes after liver transplantation, in Japan.

Results

Forty‐five of 64 institutions (70%) responded to our initial investigation. Between January 2001 and December 2015, 6627 liver transplantations were performed in these 45 institutions, with 19 cases (0.3%) of incidental intrahepatic cholangiocarcinoma reported from 12 transplant centers. Six cases were diagnosed as hepatocellular carcinoma preoperatively. The 1‐, 3‐, and 5‐year recurrence‐free survival rates were 79%, 45%, and 45%, respectively. Tumor recurrence after liver transplantation was found in 10 patients (53%). The 1‐, 3‐, and 5‐year overall survival rates were 79%, 63%, and 46%, respectively.

Conclusions

Intrahepatic cholangiocarcinoma at liver transplantation is associated with a high risk of recurrence and poor prognosis, even these tumors are detected incidentally in the explanted liver.
Association between circulating rotavirus genotypes and histo‐blood group antigens in the children hospitalized with acute gastroenteritis in Iran
Authors: Farahmand Mohammad , Jalilvand Somayeh , Arashkia Arash , Shahmahmoodi Shohreh , Afchangi Atefeh , Mollaei‐Kandelous Yaghoub , Shoja Zabihollah
Published: January 2021

Rotaviruses are the dominant cause of severe acute gastroenteritis in children under 5 years of age. Previous studies showed that some children are less susceptible to rotavirus gastroenteritis. It has been shown that this resistance depends on the rotavirus genotype and also human histo‐blood group antigens (HBGAs), which works as a receptor for rotavirus surface protein (VP4). The present study aimed to evaluate the human genetic susceptibility to rotavirus gastroenteritis in Iran and to obtain a comparative analysis between rotavirus gastroenteritis and secretor or Lewis status in case and control groups in the Iranian population. The study was performed on fecal specimens from 108 children with acute rotavirus gastroenteritis from 2015 to 2017. A total of 50 fecal specimens from children with acute gastroenteritis of unknown etiology were also used as a control group. After the genotyping of positive rotavirus cases and human HBGAs by Sanger sequencing, the phylogenetic tree analysis showed that all rotavirus strains from Iran belonged to P[II]. The most common genotype was P[8] (n = 102; 94.4%), while the remaining belonged to P[4] (n = 3; 2.8%) and P[6] (n = 3; 2.8%) genotypes. The P[8] genotype was found to be associated with secretor and Lewis positive status (p < .05).
A complementary critical appraisal on systematic reviews regarding the most efficient therapeutic strategies for the current COVID‐19 (SARS‐CoV‐2) pandemic
Authors: Kheirabadi Dorna , Haddad Fatemeh , Mousavi‐Roknabadi Razieh S. , Rezaeisadrabadi Mohammad , Dehghan Hamidreza , Fazlzadeh Aylar
Published: January 2021

Background

This critical appraisal aims to clarify which systematic reviews on COVID‐19 treatment are based on high‐value evidence. Hereby, the most profitable medicines can be suggested.

Methods

The mesh terms of "COVID‐19 drug treatment" (Supplementary Concept) and "COVID‐19 drug treatment" were sequentially utilized as search strategies in Medline and Science direct on October 18, 2020. Searches were confined to systematic reviews/meta‐analyses. The Cochrane database was searched on November 1, 2020 with "COVID." With adding up four articles from other resources, 84 systematic reviews were considered for initial screening. Finally, 22 articles fulfilled the criteria and were assessed using PRISMA guidelines.

Results

Increasing number of clinical trials from the onset of the COVID‐19 pandemic has revealed that hydroxychloroquine and chloroquine are not only profitable but also deleterious. Lopinavir/ritonavir failed to maintain their initial efficacy in improving clinical symptoms and mortality rate. Steroids and tocilizumab were suggested in patients with intensely severe symptoms. Steroids reduced mechanical ventilation and death in severely ill patients. Plasma or immunoglobulins effects are absolutely controversial. Favorable impressions of remdesivir have been relied on for the early onset of this drug. Hypotension and abnormal liver function tests were realized as its side effects. Favipiravir has resulted in a higher viral clearance than remdesivir. However, this claim needs to be proved with subsequent clinical trials.

Conclusions

Currently, remdesivir and favipiravir are advantageous drugs that should be administered in the early phases. Their side effects are not well known and need to be found in the following research projects. Steroids and tocilizumab have been considered beneficial in the cytokine storm phase.
Aural and Visual Detection of Greater Sage‐Grouse Leks: Implications for Population Trend Estimates
Authors: Riley Ian P. , Conway Courtney J. , Stevens Bryan S. , Roberts Shane B.
Published: January 2021

Counts of greater sage‐grouse (Centrocercus urophasianus) at leks have been used in harvest management, Endangered Species Act listing decisions, and land management policies for over half a century. Lek count sampling methods focus on counting male sage‐grouse at known leks, primarily those observed visually from roads or vantage points, but leks are likely missed that are unknown prior to the survey and are difficult to detect while driving between known lek sites. One way to ameliorate this shortfall may be to conduct short point‐count surveys at multiple stops along lek‐survey routes or while driving between lek counts, thereby detecting newly established or unknown leks. To evaluate the feasibility of this approach, we estimated aural and visual detection probability of active sage‐grouse leks during 1‐minute point‐count surveys at known distances and examined the effects of environmental factors on aural lek detection in southern Idaho, USA, 2016–2017. Our results demonstrate that field observers can aurally detect sage‐grouse leks at approximately 3 times greater distances compared to detecting leks visually. The probability of hearing an active lek was highest near the peak of male and female attendance (8 Apr), within an hour of sunrise, on relatively calm and cold days, when the observer was at a higher elevation relative to the lek, and during conditions with no background noise. Detection probability declined with distance and the probability of aural detection was 0.59 at 1 km from a lek when other variables were held at their means. Hence, conducting ≥3 1‐minute surveys along a lek route would be expected to detect ≥93% of all leks within 1.5 km of each survey under the average environmental conditions in our study. Our results suggest that surveys could greatly improve detection of unknown or newly established leks and can facilitate a more accurate assessment of sage‐grouse population trends through lek counts. Moreover, our results demonstrate how environmental factors influence the detection of leks during surveys, and therefore which variables should be considered for inclusion in any future revisions of lek count protocols or in analyses of lek count data. © 2021 The Wildlife Society.
On universal modules with pure embeddings
Authors: Kucera Thomas G. , Mazari‐Armida Marcos
Published: January 2021

We show that certain classes of modules have universal models with respect to pure embeddings: Let R be a ring, T a first‐order theory with an infinite model extending the theory of R‐modules and (where ⩽pp stands for “pure submodule”). Assume has the joint embedding and amalgamation properties. If or , then has a universal model of cardinality λ. As a special case, we get a recent result of Shelah [28, 1.2] concerning the existence of universal reduced torsion‐free abelian groups with respect to pure embeddings.

We begin the study of limit models for classes of R‐modules with joint embedding and amalgamation. We show that limit models with chains of long cofinality are pure‐injective and we characterize limit models with chains of countable cofinality. This can be used to answer [18, Question 4.25].

As this paper is aimed at model theorists and algebraists an effort was made to provide the background for both.
Notes about s‐numbers for a Sobolev type embedding of order 4 and for a higher order integral operator
Authors: Gurka Petr , Lang Jan
Published: January 2021

The main focus of this paper is on study of s‐numbers for a higher order Sobolev embedding on an interval and also for the corresponding Hardy‐type operator. Upper and lower estimates for approximation and Bernstein numbers are described and their relations with results for lower order Sobolev embeddings are discussed.
Nano‐sized precipitates in 11 % Cr ferritic‐martensitic steel after thermomechanical treatment
Authors: Cheng J. , Shen Y. , Zhou X. , Xu Z. , Fan Z.
Published: January 2021

9 %–12 % Cr ferritic/martensitic steels with a good long‐term creep strength at temperatures up to 650 °C and higher are being developed in order to increase steam temperature of coal‐fired power plants.Thermomechanical treatment can effectively enhance the mechanical properties of high‐Cr ferritic/martensitic steels mainly due to plenty of nano‐sized precipitates produced by thermomechanical treatment. Nano‐sized precipitates in an 11 % Cr ferritic/martensitic steel produced by a thermomechanical treatment, including warm rolling at 650 °C plus tempering at 650 °C for 1 h, were investigated by transmission electron microscopy. The average size of precipitates in the steel after the thermomechanical treatment was determined to be about 30 nm in diameter, which is only one‐third of the average size of precipitates in the steel with the normalized and tempered condition. A large number of Cr‐rich precipitates having an average diameter of about 25 nm in the steel produced by the thermomechanical treatment were identified as Cr‐rich M2C carbide with a hexagonal crystal structure, rather than M23C6 or MX phase. The plenty of nano‐sized Cr‐rich M2C carbides were dominant phase in the steel after the thermomechanical treatment. The reason why prior precipitate phase formed in the steel during the thermomechanical treatment was Cr‐rich M2C carbide is also discussed.
Neuropsychiatric Symptoms Are Associated with Dementia in Parkinson's Disease but Not Predictive of it
Authors: Horne Kyla‐Louise , MacAskill Michael R. , Myall Daniel J. , Livingston Leslie , Grenfell Sophie , Pascoe Maddie J. , Young Bob , Shoorangiz Reza , Melzer Tracy R. , Pitcher Toni L. , Anderson Tim J. , Dalrymple‐Alford John C.
Published: January 2021

Background

Neuropsychiatric symptoms in Parkinson's disease (PD) may increase dementia (PDD) risk. The predictive value of these symptoms, however, has not been compared to clinical and demographic predictors of future PDD.

Objectives

Determine if neuropsychiatric symptoms are useful markers of PDD risk.

Methods

328 PD participants completed baseline neuropsychiatric and MDS‐Task Force‐Level II assessments. Of these, 202 non‐demented individuals were followed‐up over a four‐years period to detect conversion to PDD; 51 developed PDD. ROC analysis tested associations between baseline neuropsychiatric symptoms and future PDD. The probability of developing PDD was also modeled as a function of neuropsychiatric inventory (NPI)‐total score, PD Questionnaire (PDQ)‐hallucinations, PDQ‐anxiety, and contrasted to cognitive ability, age, and motor function. Leave‐one‐out information criterion was used to evaluate which models provided useful information when predicting future PDD.

Results

The PDD group experienced greater levels of neuropsychiatric symptoms compared to the non‐PDD groups at baseline. Few differences were found between the PD‐MCI and PD‐N groups. Six neuropsychiatric measures were significantly, but weakly, associated with future PDD. The strongest was NPI‐total score: AUC = 0.66 [0.57–0.75]. There was, however, no evidence it contained useful out‐of‐sample predictive information of future PDD (delta ELPD = 1.8 (SD 2.5)); Similar results held for PDQ‐hallucinations and PDQ‐anxiety. In contrast, cognitive ability (delta ELPD = 36 (SD 8)) and age (delta ELPD = 11 (SD 5)) provided useful predictive information of future PDD.

Conclusions

Cognitive ability and age strongly out‐performed neuropsychiatric measures as markers of developing PDD within 4 years. Therefore, neuropsychiatric symptoms do not appear to be useful markers of PDD risk.
Preservation of laryngeal function through reconstruction of the supraglottis and thyrohyoid membrane with a chimeric anterolateral thigh flap after supraglottic laryngectomy: A case report and literature review
Authors: Werner Jonas , Scaglioni Mario F. , Ko Seo S. , Rajan Gunesh P.
Published: January 2021

Supraglottic laryngectomy offers a treatment option in laryngeal cancer confined to the supraglottis with the aim to preserve laryngeal functions. Current reconstruction modalities face the challenges of restoring swallow function and preventing chronic aspiration. In this report, we present for the first time a case in which the thyrohyoid membrane and supraglottis were reconstructed using a chimeric anterolateral thigh (ALT) flap. Horizontal supraglottic laryngectomy was performed in a 70‐year‐old male patient with recurrent supraglottic laryngeal cancer after primary radiotherapy. The chimeric ALT flap used for reconstruction measured 7 x 20 cm and was based on two perforators, allowing it to be divided in two parts. The larger deepithelialized fasciocutaneous paddle was used for the reconstruction of the supraglottic defect and the smaller skin paddle was utilized as monitor flap and for neck resurfacing. The chimeric ALT flap was anastomosed to the superior thyroid artery and to a branch of the internal jugular vein. The postoperative recovery was uneventful. Laryngeal functions, including an unimpaired voice, could be preserved. Six months postoperatively, the patient showed no signs of chronic aspiration or tumor recurrence. Using a chimeric ALT free flap for reconstruction after horizontal supraglottic laryngectomy may prevent chronic aspiration through restoration of larynx elevation, mobility, and thus airway protection during deglutition due to increased supraglottic bulk.
High gain, low radar cross‐section, and left hand circularly polarized antenna array based on metamaterial inspired elements
Authors: Rahman Saeed Ur , Cao Qunsheng , Khan Zakir , Deng Hai , Ullah Naveed
Published: January 2021

In this research work, a wideband metamaterial‐inspired circularly polarized antenna array is designed. The designed antenna array has a low radar cross‐section (RCS) but high gain. The basic element of the planar array is analyzed as a dual‐band electromagnetic absorber. Under normal incidence, the designed basic element has two absorbing peaks at 3.6 and 11.2 GHz. Further, four elements of the 4 × 4 elements array are connected to the feeding network through metallic vias. The feeding network is designed on the bottom layer. The circular polarization is archived by feeding the cross shape metallic resonator at two feed points, in a manner that there is a 90° time phase difference between the fields of two. It is shown that a good axial ratio is obtained over a wideband. This design method simultaneously validates high gain antenna performance and also meets the conditions of low‐RCS.
An ultra‐wideband wide‐scanning phased array of double‐ridged horn elements with slant polarized characteristics
Authors: Yang Ya‐Bing , Zhang Fu‐Shun , Zhao Jiao‐Cheng , Zhang Chen‐Guang
Published: January 2021

In this paper, an ultra‐wideband wide‐scanning phased array with slant polarized characteristics is proposed. The antenna array mainly consists of 16 double‐ridged horn elements to form a one‐dimensional linear array in the azimuth plane. Each element is fed by a SSMA connector and connected to the T/R module through a low‐loss flexible coaxial cable. To obtain slant polarized performance, a multiscreen slant polarizer is adopted and placed at the radiation aperture of the antenna array, which consists of three layers periodic metallic strips. Each layer of the polarizer is etched on a thin dielectric substrate, and adjacent layers are separated by a low dielectric constant foam. A 1 × 16 array prototype has been designed, fabricated, and tested. The measured results indicate that the proposed slant polarized phased array has a desirable 3‐octave bandwidth, a excellent ±45° wide‐scanning capability, and a stable gain over the 6–18 GHz band.
Development of a novel framework to evaluate the localization accuracy of tomosynthesis‐guided breast biopsy units
Authors: Nosrati Reyhaneh , Zhang Da , MacDougall Robert D , Phillips Jordana , Palmer Matthew R
Published: January 2021

Purpose

To develop a scheme to quantitatively assess localization accuracy of tomosynthesis‐guided vacuum‐assisted breast biopsy apparatus.

Methods

A phantom containing a metallic pellet on a flexible plastic shaft was constructed and was tested in cranio‐caudal (CC) and lateral (LAT) arm biopsy geometries following the standard clinical breast biopsy workflow. Three points were manually digitized on tomosynthesis images including: the center of the target, and the tip of the needle in pre‐ and postfire positions. The needle trajectory was determined and four error metrics were defined: (1) stroke length error (difference between the nominal and measured stroke lengths); (2) Euclidian distance between the target and center of trough (i.e., aperture); (3) longitudinal distance between target and center of trough; and (4) lateral distance between target and needle. The proposed methodology was also evaluated on a breast gel phantom and the complete biopsy procedure, including vacuum‐assisted biopsy was performed.

Results

Three biopsy geometries were investigated: (i) LAT arm on a prone table unit (Hologic, Affirm Prone), (ii) CC‐ and (iii) LAT arm in an upright unit (Hologic Affirm Upright). Both biopsy units passed the vendor‐provided daily localization accuracy test, with <1 mm nominal error in each dimension. The aforementioned error metrics (1) to (4) were (0.6, 1.8, 0.4, 1.7) mm, (0.4, 4.2, 4.1, 1.1) mm, and (0.3, 2.4, 0.7, 2.3) mm, respectively, for geometry‐I, ‐II, and ‐III. The gel phantom was tested on the upright unit with lateral arm and the error metrics (1) to (4) were 0.4, 2.5, 0.8, and 2.4 mm respectively.

Conclusions

A framework was developed to evaluate the tomosynthesis‐guided breast biopsy localization error, allowing quantitative comparisons between different systems and biopsy configurations. The proposed framework can also be extended to the stereotactic breast biopsy units. We suggest that a quantitative tolerance level for localization accuracy of breast biopsy units be established.
Permanent encoding of nano‐ to macro‐scale hierarchies of order from evaporative magnetic fluids
Authors: Zhong Tianyu , Andrews Mark , Fournier Patrick , Dion Maxime
Published: January 2021

Magnetic field‐directed assemblies of magnetic nanoparticles (MNPs) in ferrofluids exhibit complex interconvertible metastable patterns and structures. Formally, ferrofluid patterns are unstable – they disappear when the magnetic field is removed. The present study shows that ferrofluid patterns can be “trapped” as kinetically stable structures that encode a surprising degree of morphological detail over nanometer to millimeter length scales. An external magnetic field is used to direct assembly of oleic acid‐decorated magnetite (Fe3O4) nanoparticles to make spike and labyrinthine patterns in volatile host solvents of heptane, octane and nonane. Solvent evaporation coupled with increases in sample magnetization drive pattern formation and its permanent recording. Use of a crosslinking siloxane polymer host yields remarkably different material responses. From the trapped states in both fluid systems, previously unreported hierarchies of order emerge in nanocomposite spike structures that also exhibit orientational and magnetic anisotropy. The possibility of designing hierarchical matter from initially uncorrelated MNPs is demonstrated by a directed solid‐state transformation of the magnetic nanocomposite; the spikes template memory of their origin onto the transformation products.
The effectiveness of skeletal age‐estimation in the reconstruction of population survivorship in post‐medieval Dublin
Authors: Clark Melissa A.
Published: January 2021

Bioarchaeologists have long used age estimates from skeletal remains to draw conclusions about past lifeways and sociobiological phenomena such as health, stress, fertility, and frailty, among others. However, the estimation of age from skeletal remains is complicated by a multitude of well‐documented challenges including age mimicry, variation in degeneration, preservation, and accuracy between anatomical regions, individuals, and populations. The application of transition analysis to bioarchaeological age estimation was introduced nearly two decades ago to address some of these challenges, and the newest version promise further improvements. However, given the time lag between the introduction of a new technology and its adoption, continued evaluation of existing methods remains important. The purpose of this study was to evaluate the effectiveness of skeletal age‐at‐death estimation through transition analysis in the reconstruction of population survivorship in 18th century Dublin, Ireland. It was hypothesized that there would be no differences between the survival distributions calculated from 18th‐century parish records and survival distributions estimated from skeletal remains rom approximately the same time and location. Results show that survivorship estimated from transition analysis was approximately equal to the survivorship calculated from burial records in early‐ to mid‐adulthood, despite the fact that the samples do not represent the same individuals. However, transition analysis consistently produced higher survival curves in later adulthood, despite the lower socioeconomic statuses of the individuals represented in the skeletal sample relative to the individuals in the burial records, though these differences were not statistically significant for females. These findings suggest that bioarchaeologists should continue to exercise caution when drawing conclusions about populations based on skeletons.
Reconsidering Dexamethasone for Antiemesis when Combining Chemotherapy and Immunotherapy
Authors: Janowitz Tobias , Kleeman Sam , Vonderheide Robert H.
Published: January 2021

Whether the immune suppressive action of glucocorticoid steroids, such as dexamethasone, might reduce the benefits of cancer immunotherapy has long been a concern. Observations that established tumor regressions in response to immune checkpoint inhibitors (ICIs) often persist, despite the use of steroids to mitigate ICI-related autoimmune breakthrough, are not sufficiently reassuring, because these observations do not address the potential blunting of immune priming at the initiation of ICI therapy. With increasing indications for ICI in combination with chemotherapy, this issue merits reconsideration. Professional society guidance advises that dexamethasone should be used as first-line prophylaxis for nausea and vomiting in patients receiving ICI and highly emetogenic chemotherapy combination regimens. Here, we review the availability of data on this subject and propose an alternative approach focused on the adoption of steroid minimization or sparing for prophylaxis of nausea until the underlying immune biology is better understood.
A new approach for kinetic modeling and optimization of rubber molding
Authors: Bera Oskar , Pavličević Jelena , Ikonić Bojana , Lubura Jelena , Govedarica Dragan , Kojić Predrag
Published: January 2021

Although extensive research has been carried out on the understanding of the complex vulcanization process, the influence of reversion through exposure time and temperature on the vulcanization degree remains unclear. Therefore, the main aim of this study was a novel optimization approach that can help the industrial practitioners to select the optimal operating parameters, exposure time, and molding temperature, to achieve desired vulcanization degree of selected product. Spheres of four different diameters (2.5, 5, 10, and 20 cm) were selected as test geometry for simulation and optimization of rubber molding. Obtained vulcanization rheometer data for commercially available rubber blend (NR/SBR) were fitted by a new modeling approach, dividing vulcanization curve into two fitting sets: curing and reversion. The heat transfer equations for chosen geometry were coupled with proposed kinetic model. A new temperature‐dependent kinetic parameter x, as the maximal reversion degree, was introduced, enabling determination of the lowest operating molding temperature (Tmin = 132.36 °C), preventing high reversion and overheating of the rubber product. The final optimization goal was assessment of the optimal temperature and vulcanization time dependence on the rubber products dimensions. Proposed models have precise prediction with R2 values greater than 0.8328 and MAPE less than 2.3099%.
Inherently ill‐defined nature of waste: Fatal outdoor poisoning of hazmat waste collection driver ‐ lessons learned
Authors: Hedlund Frank Huess , Aldrich Per Tybjerg
Published: January 2021

The paper examines the fatal poisoning of a vacuum truck driver who inadvertently mixed sulfuric and formic acid waste, which reacted to produce carbon monoxide gas in the truck's tank. The case highlights multiple systemic issues in the chemical waste disposal industry which may lead to repeat accidents. The paper argues that an ill‐defined composition is an intrinsic property of any waste. Therefore, the guiding safety principle should be to avoid mixing and minimize manual handling to the widest extent possible. Transport for disposal of hazmat waste in non‐conforming 1000‐L pallet tanks presents two unattractive options: (a) A vacuum truck is a simple and cost‐effective solution but entails chemical reactivity hazards upon mixing. (b) A 1:1 transfer of the contents to new compliant containers avoids mixing hazards but introduces manual handling hazards. The option of placing the pallet tank inside another approved enclosure appears unavailable in practice. Currently, the overall best option in many cases may be to transport the waste in the formally non‐compliant pallet tanks, by having guidelines for when and how to relax compliance requirements. The paper argues that the current ADR regulatory regime and the hazmat disposal industry offer insufficient support in making safer options available.
Anti‐colon cancer activity tracking isolation of peptide from ginseng leaves and potential mechanisms evaluation in vitro and in vivo
Authors: Liu Zhuo , Liu Xiaolei , Li Wei , Luo Qiang , Liu Jie , Wang Dongxin
Published: January 2021

The ginseng has been used for over hundred years, in the belief of promoting longevity. However, the anticancer activity of ginseng leaf peptide (GP) has been never explored. In current study, we isolated the GPs and explored the anti‐colon cancer activity in vitro and in vivo. MTT results showed that the GP‐1 (GP‐1~FKEHGY) performed most antiproliferative activity against colon cancer CT‐26 cells with an IC50 of 86.4 ± 9.46 μM (48 h). Further study indicated that GP‐1 activated the caspases, regulated the p53/murine double minute 2 (MDM2) state, and induced the CT‐26 cells apoptosis in a mitochondrial pathway. Meanwhile, the GP‐1 arrested the CT‐26 cells in G0/G1 phase accompanied with cyclin expression regulation. In addition, GP‐1 significantly suppressed the tumor growth and induced the tumor cells apoptosis in vivo. Notably, the GP‐1 would be a potential anti‐colon cancer candidate.
Biosaur: An open‐source Python software for liquid chromatography–mass spectrometry peptide feature detection with ion mobility support
Authors: Abdrakhimov Daniil A. , Bubis Julia A. , Gorshkov Vladimir , Kjeldsen Frank , Gorshkov Mikhail V. , Ivanov Mark V.
Published: January 2021

RATIONALE

One of the important steps in initial data processing of peptide mass spectra is the detection of peptide features in full‐range mass spectra. Ion mobility offers advantages over previous methods performing this detection by providing an additional structure‐specific separation dimension. However, there is a lack of open‐source software that utilizes these advantages and detects peptide features in mass spectra acquired along with ion mobility data using new instruments such as timsTOF and/or FAIMS‐Orbitrap.

METHODS

Recently, a utility called Dinosaur was presented, which provides an efficient way for feature detection in peptide ion mass spectra. In this work we extended its functionality by developing Biosaur software to fully employ the additional information provided by ion mobility data. Biosaur was developed using the Python 3.8 programming language.

RESULTS

Biosaur supports the processing of data acquired using mass spectrometers with ion mobility capabilities, specifically timsTOF and FAIMS. In addition, it processes mass spectra obtained in negative ion mode and reports cosine correlation table for peptide features which is useful for differentiation between in‐source fragments and semi‐tryptic peptides.

CONCLUSIONS

Biosaur is a utility for detecting peptide features in liquid chromatography–mass spectra with ion mobility and negative ion supports. The software is distributed with an open‐source APACHE 2.0 license and is freely available on Github: https://github.com/abdrakhimov1/Biosaur.
A new actuator fault‐tolerant control for Lipschitz nonlinear system using adaptive sliding mode control strategy
Authors: Ijaz Salman , Chen Fuyang , Tariq Hamayun Mirza
Published: January 2021

This article proposed a new adaptive integral sliding mode (ISM) based fault‐tolerant control (FTC) strategy to solve the actuator's faults and failures compensation problem for the class of Lipschitz nonlinear systems. A nominal state feedback virtual control law is designed first to stabilize the Lipschitz nonlinear system and to attain the desired nominal performance. To cater for the effect of faults and failures, the control allocation (CA) scheme reorganizes the virtual input signals among the healthy redundant actuators based on actuator's effectiveness level. Then, a nonlinear adaptive integral sliding mode controller (ISMC) is incorporated with the CA scheme to compensate for unknown disturbance and uncertainties effect that arises in the system by virtue of actuator faults/failures and error in fault estimation . An effective synthesis procedure is adopted to ensure the closed‐loop stability condition using linear matrix inequality (LMI) optimization. Finally, the FTC scheme is tested to achieve maneuvering control of coaxial octorotor unmanned aerial vehicle (UAV) system. Simulations are performed on the nonlinear system at different actuator faults/failures combinations. Moreover, the effect of wind‐gust, parameter variations, estimated state feedback and sensor noise are considered in nonlinear simulations. Finally, the results obtained during faults/failures are compared with the nominal condition and fixed ISMC based CA scheme.
Efficient Synthesis of Phosphorus/Nitrogen‐Containing Chrysin Derivatives via Classic Reactions
Authors: Zeng Ziyi , Liu Shuang , Luo Wenjun , Liang Jiaxin , Peng Ai‐Yun
Published: January 2021

Chrysin is a widely distributed natural flavonoid with broad biological activities, but its poor bioavailability and insufficient efficacy limit its clinical applications. Based on prodrug and combination principles, we designed and synthesized sixteen new chrysin derivatives containing phosphonate, phosphoramidate and primary amine groups with different spaces at C‐7 position of chrysin in 66–93 % yields. The synthetic strategies involve the use of classic Arbuzov, Staudinger‐phosphite and Staudinger‐reduction reactions. The derivatives were herein prepared from easily available starting materials under mild conditions and fully characterized by 1H/13C/31P NMR, IR, MS, elemental analysis or HRMS.
Forecasting hurricane‐related power outages via locally optimized random forests
Authors: Coleman Tim , Dorn Mary Frances , Kaufeld Kim , Mentch Lucas
Published: January 2021

Standard supervised learning procedures are validated against a test set that is assumed to have come from the same distribution as the training data. However, in many problems, the test data may have come from a different distribution. We consider the case of having many labeled observations from one distribution, P1, and wanting to make predictions at unlabeled points that come from P2. We combine the high predictive accuracy of random forests with an importance sampling scheme, where the splits and predictions of the base trees are done in a weighted manner, which we call locally optimized random forests. These weights correspond to a non‐parametric estimate of the likelihood ratio between the training and test distributions. To estimate these ratios with an unlabeled test set, we make the covariate shift assumption, where the differences in distribution are only a function of the training distributions. This methodology is motivated by the problem of forecasting power outages during hurricanes. The extreme nature of the most devastating hurricanes means that typical validation set ups will produce models that underestimate their devastating effects. Our method provides a data‐driven means of adapting a machine learning method to deal with extreme events.
Weighted empirical likelihood for heteroscedastic varying coefficient partially non‐linear models with missing data
Authors: Fan Guo‐Liang , Wang Lu‐Lu , Xu Hong‐Xia
Published: January 2021

In this article, a weighted empirical likelihood technique for constructing the empirical likelihood confidence regions is applied to study the heteroscedastic varying coefficient partially non‐linear models with missing response data. We first provide an estimator of the error variance based on the Nadaraya–Watson kernel estimation method. Then a weighted empirical log‐likelihood ratio of the unknown parameter is constructed based on the inverse probability weighted technique. The maximum empirical likelihood (MEL) estimator of the unknown parameter is obtained. Further, a weighted empirical log‐likelihood ratio of the varying coefficient function is introduced based on the MEL estimator and the inverse probability weighted method. The limiting distributions of the resulting statistics for both the unknown parameter and varying coefficient function are shown to have the standard chi‐squared distribution. A simulation study and a real data set example are undertaken to investigate the finite sample performance of the proposed methods.
Eigenvalue bifurcation in doubly nonlinear problems with an application to surface plasmon polaritons
Authors: Dohnal Tomáš , Romani Giulio
Published: January 2021

We consider a class of generally non-self-adjoint eigenvalue problems which are nonlinear in the solution as well as in the eigenvalue parameter (“doubly” nonlinear). We prove a bifurcation result from simple isolated eigenvalues of the linear problem using a Lyapunov–Schmidt reduction and provide an expansion of both the nonlinear eigenvalue and the solution. We further prove that if the linear eigenvalue is real and the nonlinear problem$${\mathcal {PT}}$$PT-symmetric, then the bifurcating nonlinear eigenvalue remains real. These general results are then applied in the context of surface plasmon polaritons (SPPs), i.e. localized solutions for the nonlinear Maxwell’s equations in the presence of one or more interfaces between dielectric and metal layers. We obtain the existence of transverse electric SPPs in certain$${\mathcal {PT}}$$PT-symmetric configurations.
The promise of stem cell-derived islet replacement therapy
Authors: Melton Douglas
Published: January 2021

Present-day treatments for people that are insulin dependent require multiple insulin injections, sometimes with an insulin pump, coupled with regular blood glucose monitoring. The availability of modified insulins, each with peaks of activity at varying times, has improved diabetes management. On the other hand, there have been impressive results leading to insulin independence by transplantation of cadaveric islets coupled with immune suppression. This review focuses on the possibility of treating diabetes with cellular transplants, specifically with the use of pluripotent stem cells, to produce a virtually unlimited and uniform supply of human islet-like clusters by directed differentiation. Prospects for improving the in vitro differentiation of human endocrine cells for the study of endocrine function and their possible clinical uses are also discussed.

Graphical abstract
Restricted kinematic alignment leads to uncompromised osseointegration of cementless total knee arthroplasty
Authors: Laforest Guillaume , Kostretzis Lazaros , Kiss Marc-Olivier , Vendittoli Pascal-André
Published: January 2021

Purpose

While kinematic alignment (KA) total knee arthroplasty (TKA) with cemented implants has been shown to provide equivalent or better results than mechanical alignment, its combination with cementless fixation has not yet been documented. The purpose of this study is to report (1) revision rate and causes, (2) clinical results based on patient report outcome measures (PROMs), and (3) radiological signs of implant dysfunction in patients with an uncemented TKA implanted with restricted KA (rKA), after a minimum follow-up of 2 years.

Methods

This study included the first 100 consecutive uncemented cruciate retaining TKAs implanted between November 2015 and February 2018 by a single surgeon following rKA principles. At last follow-up, all adverse events and PROMs assessed by WOMAC, KOOS, and FJS scores were documented. Radiographic evaluation was performed to identify signs of implant loosening.

Results

After a mean follow-up of 49 months (32, 60), no implant revision was performed for aseptic loosening. Three revisions were performed: one for malalignment, one for a deep infection, and one for instability. The mean WOMAC score was 20.1 (0–79, 21.3), the mean KOOS score was 71.5 (19.0–96.6, 19.8), and the mean FJS score was 65.9 (0–100, 29.6). No radiological evidence of implant aseptic loosening or osteolysis was identified.

Conclusion

This study shows that in 99% of our cases, rKA combined with the tested cementless TKA implant allowed for adequate secondary fixation and good functional outcomes in the short term. Favourable mid- to long-term implant survivorship is anticipated.

Level of evidence

III.
Safety of Transseptal Puncture for Access to the Left Atrium in Infants and Children
Authors: Müller Matthias J. , Backhoff David , Schneider Heike E. , Dieks Jana K. , Rieger Julia , Krause Ulrich , Paul Thomas
Published: January 2021

Transseptal puncture (TSP) is a standard procedure to obtain access to the left heart. However, data on TSP in infants and children particularly with congenital heart defects (CHD) is sparse. Safety and efficacy of TSP in infants and children < 18 years with normal cardiac anatomy and with CHD were assessed. 327 TSP were performed in a total of 300 individuals < 18 years from 10/2002 to 09/2018 in our tertiary pediatric referral center. Median age at TSP was 11.9 years (IQR 7.8–15; range: first day of life to 17.9 years). 13 subjects were < 1 year. Median body weight was 43.8 kg (IQR 26.9–60; range: 1.8–121 kg). CHD was present in 28/327 (8.6%) procedures. TSP could be successfully performed in 323/327 (98.8%) procedures and was abandoned in 4 procedures due to imminent or incurred complications. Major complications occurred in 4 patients. 3 of these 4 subjects were ≤ 1 year of age and required TSP for enlargement of a restrictive atrial septal defect in complex CHD. Two of these babies deceased within 48 h after TSP attempt. The third baby needed urgent surgery in the cath lab. Pericardial effusion requiring drainage was noted in the forth patient (> 1 year) who was discharged well later. Minor complications emerged in 5 patients. The youngest of these individuals (0.3 years, 5.8 kg) developed small pericardial effusion after anterograde ballon valvuloplasty for critical aortic stenosis. The remaining 4/5 patients developed small pericardial effusion after ablation of a left-sided accessory atrioventricular pathway (6.1–12.2 years, 15.6–34.0 kg). TSP for access to the left heart was safe and effective in children and adolescents > 1 year of age. However, TSP was a high-risk procedure in small infants with a restrictive interatrial septum with need for enlargement of interatrial communication.
Intra‐Abdominal Hemorrhage Control: The Need for Routine Four‐Quadrant Packing Explored
Authors: Jakob Dominik A. , Liasidis Panagiotis , Schellenberg Morgan , Matsushima Kazuhide , Lam Lydia , Demetriades Demetrios , Inaba Kenji
Published: January 2021

Background

Routine four‐quadrant packing (4QP) for hemorrhage control immediately upon opening is a standard practice for acute trauma laparotomy. The aim of this study was to evaluate the utility of 4QP for bleeding control in acutely injured patients undergoing trauma laparotomy.

Methods

Retrospective single‐center study (01/2015–07/2019), including adult patients who underwent trauma laparotomy within 4 h of admission. Only patients with active intra‐abdominal hemorrhage, defined as bleeding within the peritoneal cavity or expanding retroperitoneal hematoma, were considered for analysis. Bleeding sources were categorized anatomically: liver/retrohepatic inferior vena cava (RIVC), spleen, retroperitoneal zones 1, 2 and 3, mesentery and others. Hemorrhage was further categorized as originating from a single bleeding site (SBS) or from multiple bleeding sites (MBS). The effectiveness of directed versus 4QP was evaluated for bleeding from the liver/RIVC, spleen and retroperitoneal zone 3, areas that are potentially compressible. Directed packing was defined as indicated if the bleeding was restricted to one of the anatomic sites suitable for packing, 4QP was defined as indicated if ≥ 2 of the anatomic sites suitable for packing were bleeding.

Results

During the study time frame, 924 patients underwent trauma laparotomy, of which 148 (16%) had active intra‐abdominal hemorrhage. Of these, 47% had a SBS and 53% had MBS. The liver/RIVC was the most common bleeding source in both patients with SBS (42%) and in patients with MBS (54%). According to our predefined indications, 22 of 148 patients (15%) would have benefitted from initial 4QP, 90 of 148 patients (61%) from directed packing and 36 of 148 patients (24%) packing would not have been of any value.

Conclusion

Routine four‐quadrant packing is frequently practiced. However, this is only required in a small proportion of patients undergoing trauma laparotomy. Directed packing can be equally effective, saves time and decreases the risk of iatrogenic injury from unnecessary packing.