bluuebunny/crossref_metadata_2025 huggingface dataset:
Interleukin‐1β–Activated Microvascular Endothelial Cells Promote DC‐SIGN–Positive Alternatively Activated Macrophages as a Mechanism of Skin Fibrosis in Systemic Sclerosis
Authors: Laurent Paôline , Lapoirie Joelle , Leleu Damien , Levionnois Emeline , Grenier Cyrielle , Jurado‐Mestre Blanca , Lazaro Estibaliz , Duffau Pierre , Richez Christophe , Seneschal Julien , Pellegrin Jean‐Luc , Constans Joel , Schaeverbeke Thierry , Douchet Isabelle , Duluc Dorothée , Pradeu Thomas , Chizzolini Carlo , Blanco Patrick , Truchetet Marie‐Elise , Contin‐Bordes Cécile ,   Fédération Hospitalo‐Universitaire ACRONIM and the Centre National de Référence des Maladies Auto‐Immunes Systémiques Rares de l'Est et du Sud‐Ouest (RESO)
Published: December 2021

Objective

To characterize the role of interleukin‐1β (IL‐1β) and microvascular endothelial cells (MVECs) in the generation of alternatively activated macrophages in the skin, and to explore their role in the development of skin fibrosis in patients with systemic sclerosis (SSc; scleroderma).

Methods

Conditioned medium prepared with MVECs purified from the skin of healthy donors and the skin of SSc patients was used to generate monocyte‐derived macrophages. Flow cytometry, multiplex protein assessment, real‐time quantitative polymerase chain reaction, and tissue immunofluorescence were used to characterize MVEC‐induced polarization of alternatively activated macrophages. Coculture experiments were conducted to assess the role of MVEC‐induced alternatively activated macrophages in fibroblast activation. Alternatively activated macrophages were characterized in the skin of healthy donors and SSc patients using multiparametric immunofluorescence and multiplex immunostaining for gene expression. Based on our in vitro data, we defined a supervised macrophage gene signature score to assess correlation between the macrophage score and clinical features in patients with SSc, using the Spearman's test.

Results

IL‐1β–activated MVECs from SSc patients induced monocytes to differentiate into DC‐SIGN+ alternatively activated macrophages producing high levels of CCL18, CCL2, and CXCL8 but low levels of IL‐10. DC‐SIGN+ alternatively activated macrophages showed significant enhancing effects in promoting the production of proinflammatory fibroblasts and were found to be enriched in perivascular regions of the skin of SSc patients who had a high fibrosis severity score. A novel skin transcriptomic macrophage signature, defined from our in vitro findings, correlated with the extent of skin fibrosis (Spearman's r = 0.6, P = 0.0018) and was associated with early disease manifestations and lung involvement in patients with SSc.

Conclusion

Our findings shed new light on the vicious circle implicating unabated IL‐1β secretion, MVEC activation, and the generation of DC‐SIGN+ alternatively activated macrophages in the development of skin fibrosis in patients with SSc.
Impact of age on treatment response in men with prostate cancer treated with radiotherapy
Authors: Bryant Alex K. , Nelson Tyler J. , McKay Rana R. , Kader A. Karim , Parsons J. Kellogg , Einck John P. , Kane Christopher J. , Sandhu Ajay P. , Mundt Arno J. , Murphy James D. , Rose Brent S.
Published: December 2021

Objective

To analyse the effect of age at diagnosis on clinical outcomes of localized prostate cancer (PCa) treated with radiation therapy.

Subjects and methods

We identified 12 784 patients with intermediate‐ or high‐risk localized PCa treated with radiation therapy (RT) and neoadjuvant androgen deprivation therapy (ADT) between 2000 and 2015 from nationwide Veterans Affairs data. Patients were grouped into three age categories (≤59, 60–69, and ≥70 years old). Outcomes included immediate PSA response (3‐month post‐RT PSA and 2‐year PSA nadir, grouped into <0.10 ng/ml, 0.10–0.49 ng/ml, and ≥0.50 ng/ml), biochemical recurrence, and PCa‐specific mortality. Multivariable regression models included ordinal logistic regression for short‐term PSA outcomes, Cox regression for biochemical recurrence, and Fine‐Gray competing risks regression for PCa‐specific mortality.

Results

A total of 2136 patients (17%) were ≤59 years old at diagnosis, 6107 (48%) were 60–69 years old, and 4541 (36%) were ≥70 years old. Median follow‐up was 6.3 years. Younger age was associated with greater odds of higher 3‐month PSA group (≤59 vs. ≥70: adjusted odds ratio [aOR] 1.90, 95% CI 1.64–2.20; p < 0.001) and higher 2‐year PSA nadir group (≤59 vs. ≥70: aOR 1.89, 95% CI 1.62–2.19, p < 0.001). Younger age was associated with greater risk of biochemical recurrence (≤59 vs. ≥70: adjusted hazard ratio 1.45, 95% CI 1.26–1.67, p < 0.001) but not PCa‐specific mortality (p = 0.16).

Conclusion

In a large nationwide sample of US veterans treated with ADT and RT for localized PCa, younger age was associated with inferior short‐term PSA response and higher risk of biochemical recurrence.
Preliminary findings on the effects of medication advocacy and daily behavior ratings on prescriber behavior
Authors: Coon Jodi C. , Rapp John T. , Bush Helena , Ramey Erica S.
Published: December 2021

Over a 1‐year period, we trained caregivers to employ a color‐coded daily behavior rating system whereby green denoted a high level of appropriate behavior, yellow denoted a mix of some appropriate behavior and mild problem behavior, and red denoted a high level of problem behavior. We then used these ratings to generate graphs that caregivers brought to their child's prescriber appointments. Preliminary data comparing unconditional and conditional probabilities from 25 prescriber visits with 12 participants indicate prescribers were most likely (a) to decrease psychotropic medication following green ratings, (b) increase psychotropic medication following red ratings, and (c) make no changes following yellow ratings. Across participants, prescribers' decisions matched the color code for 76% of trials. These preliminary findings support continued inclusion of the medication‐advocacy training component to facilitate deprescribing of psychotropic medication within our state‐funded project.
Nanoengineered biomimetic hydrogels: A major advancement to fabricate 3D‐printed constructs for regenerative medicine
Authors: Cernencu Alexandra I. , Dinu Andreea I. , Stancu Izabela C. , Lungu Adriana , Iovu Horia
Published: December 2021

Nanostructured compounds already validated as performant reinforcements for biomedical applications together with different fabrication strategies have been often used to channel the biophysical and biochemical features of hydrogel networks. Ergo, a wide array of nanostructured compounds has been employed as additive materials integrated with hydrophilic networks based on naturally‐derived polymers to produce promising scaffolding materials for specific fields of regenerative medicine. To date, nanoengineered hydrogels are extensively explored in (bio)printing formulations, representing the most advanced designs of hydrogel (bio)inks able to fabricate structures with improved mechanical properties and high print fidelity along with a cell‐interactive environment. The development of printing inks comprising organic–inorganic hybrid nanocomposites is in full ascent as the impact of a small amount of nanoscale additive does not translate only in improved physicochemical and biomechanical properties of bioink. The biopolymeric nanocomposites may even exhibit additional particular properties engendered by nano‐scale reinforcement such as electrical conductivity, magnetic responsiveness, antibacterial or antioxidation properties. The present review focus on hydrogels nanoengineered for 3D printing of biomimetic constructs, with particular emphasis on the impact of the spatial distribution of reinforcing agents (0D, 1D, 2D). Here, a systematic analysis of the naturally‐derived nanostructured inks is presented highlighting the relationship between relevant length scales and size effects that influence the final properties of the hydrogels designed for regenerative medicine.
Chiral 2‐phenyl‐3‐hydroxypropyl esters as PKC‐alpha modulators: HPLC enantioseparation, NMR absolute configuration assignment, and molecular docking studies
Authors: Linciano Pasquale , Nasti Rita , Listro Roberta , Amadio Marialaura , Pascale Alessia , Potenza Donatella , Vasile Francesca , Minneci Marco , Ann Jihyae , Lee Jeewoo , Zhou Xiaoling , Mitchell Gary A. , Blumberg Peter M. , Rossi Daniela , Collina Simona
Published: December 2021

Protein kinase C (PKC) isoforms play a pivotal role in the regulation of numerous cellular functions, making them extensively studied and highly attractive drug targets. In our previous work, we identified in racemate 1–2, based on the 2‐benzyl‐3‐hydroxypropyl ester scaffold, two new potent and promising PKCα and PKCδ ligands, targeting the C1 domain of these two kinases. Herein, we report the resolution of the racemates by enantioselective semi‐preparative HPLC. The attribution of the absolute configuration (AC) of homochirals 1 was performed by NMR, via methoxy‐α‐trifluoromethyl‐α‐phenylacetic acid derivatization (MTPA or Mosher's acid). Moreover, the match between the experimental and predicted electronic circular dichroism (ECD) spectra confirmed the assigned AC. These results proved that Mosher's esters can be properly exploited for the determination of the AC also for chiral primary alcohols. Lastly, homochiral 1 and 2 were assessed for binding affinity and functional activity against PKCα. No significative differences in the Ki of the enantiopure compounds was observed, thus suggesting that chirality does not seem to play a significant role in targeting PKC C1 domain. These results are in accordance with the molecular docking studies performed using a new homology model for the human PKCαC1B domain.
Defining quality in thyroid FNA
Authors: Renshaw Andrew A.
Published: December 2021

Combining cytologic and molecular data may provide a useful approach to defining quality in thyroid fine‐needle aspiration. The article in this issue by Gokozan and colleagues provides an excellent starting point for defining quality metrics that incorporate both cytologic and molecular results to ensure patients receive the best care.
Local to continental‐scale variation in fitness and heritability in common bean
Authors: MacQueen Alice H. , Khoury Colin K. , Miklas Phil , McClean Phillip E. , Osorno Juan M. , Runck Bryan C. , White Jeffrey W. , Kantar Michael B. , Ewing Patrick M.
Published: December 2021

Selection during plant domestication and improvement often decreases genetic variation, including variation that confers adaptation to local conditions. We report spatial and temporal variation in fitness (seed yield), local adaptation, and segregating genetic variation within three races of common bean (Phaseolus vulgaris L.) with differing domestication histories and genetic diversities. Three‐hundred and twenty‐seven common bean genotypes had seed yield measured at subsets of 70 sites across North America between 1981 and 2015, as part of the Cooperative Dry Bean Nursery (CDBN). We estimated local adaptation using the metric home field advantage (HFA) and segregating genetic variation using heritability. The Durango and Mesoamerican races (Middle American genepool) had higher‐than‐expected (p = .002) HFA, equal to up to 34 yr of average yield gains. Surprisingly, Nueva Granada (Andean genepool) and Durango yields became more heritable across the study period (p < .001), while Mesoamerican heritability decreased (p < .001). Both metrics detected diversity loss corresponding to the timings of major historical gene introgressions. Local adaptation remains an agronomically important phenomenon within some common bean races. Common bean adaptation to new conditions will be most rapid at locations with large local adaptation benefits and high heritability.
Liquid‐ and Solid‐based Separations Employing Ionic Liquids for the Recovery of Platinum Group Metals Typically Encountered in Catalytic Converters: A Review
Authors: Lanaridi Olga , Schnürch Michael , Limbeck Andreas , Schröder Katharina
Published: December 2021

The wide application range and ascending demand for platinum group metals combined with the progressive depletion of their natural resources renders their efficient recycling a very important and pressing matter. Primarily environmental considerations associated with state‐of‐the‐art recovery processes have shifted the focus of the scientific community toward the investigation of alternative recycling approaches. Within this context, ionic liquids have gained considerable attention in the last two decades chiefly sparked by properties such as tunabilty, low‐volatility, and relatively easy recyclability. In this review an understanding of the state‐of‐the‐art processes, including their drawbacks and limitations, is provided. The core of the discussion is focused on platinum group metal recovery with ionic liquid‐based systems. A brief insight in some environmental considerations related to ionic liquids is also provided while some discussion on research gaps, common misconceptions related to ionic liquids and outlook on unresolved issues could not be absent from this review.
The role of the protein tyrosine phosphatase SHP2 in ossification
Authors: Zhang Yuan , Lu Wei , Zhao Qing , Chen Jindong , Wang Tiancong , Ji Jun
Published: December 2021

SHP2, encoded by the PTPN11 gene, participates in multiple cell functions including cell proliferation, movement, and differentiation. PTPN11 loss‐of‐function and gain‐of‐function mutations are both associated with diseases, such as Noonan syndrome, whose manifestations include bone defects, suggesting a crucial role for SHP2 in the skeleton. However, the exact mechanisms by which SHP2 regulates bone development remain unclear. This review focuses on the current understanding of the regulation of SHP2 and highlights the vital roles of SHP2 in skeletal development, especially its roles in ossification. Overall, a better understanding of the functions of SHP2 in ossification will provide a new avenue to treat‐related skeletal diseases.
B‐cell modulation with anti‐CD79b antibodies ameliorates experimental autoimmune encephalitis in mice
Authors: Renner Kerstin , Neumayer Sophia , Talke Yvonne , Buchtler Simone , Schmidbauer Kathrin , Nimmerjahn Falk , Lux Anja , Winter Frederike , Salewski Jan‐Nicklas , Mack Matthias
Published: December 2021

B cells play a major role in the pathogenesis of many autoimmune diseases like MS, rheumatoid arthritis, or systemic lupus erythematosus. Depletion of B cells with anti‐CD20 antibodies is an established therapy for MS. However, total B‐cell depletion will also affect regulatory B cells that are known to suppress autoimmune responses. In our studies, we describe an alternative approach based on targeting CD79b that induces only partial B‐cell depletion and achieves therapeutic effects by B‐cell modulation. Prophylactic and therapeutic treatment with an antibody against CD79b and also a deglycosylated variant of this antibody, lacking effector function like antibody‐dependent cellular cytotoxicity or complement activation, significantly reduced the development and progression of EAE in mice. Our data show that modulation of B cells via CD79b is equally effective as almost complete B‐cell depletion with anti‐CD20 antibodies and may constitute an alternative approach to treat MS.
Gold‐Catalyzed Regioselective Oxyfluorination/Oxydifluorination vs. Diketonization of Phthalimido‐Protected Propargylamines with Selectfluor
Authors: Marsicano Vincenzo , Arcadi Antonio , Michelet Véronique
Published: December 2021

Alkyl‐ and aryl‐substituted N‐propargyl phthalimides were used as valuable building blocks for the selective formation of the corresponding α‐fluoro, β‐phthalimido ketones, α,α‐difluoro, β‐phthalimido ketones or β‐phthalimido α‐diketones by means of gold‐catalyzed oxyfluorination/oxydifluorination or dioxygenation reactions. The key factors addressing the product selectivity control were determined. The simultaneous assembly of the quinoxaline nucleus and the removal of the phthalimido‐protecting group were tested. Reaction mechanisms of the different reaction pathways are assumed.
Geometry change impact on thermal efficiency with large volumetric sensible heat storage tank
Authors: Kocijel Lino
Published: December 2021

By installation in district heating and cooling systems, large volumetric sensible heat storage tank is a technology that can reduce CO2 emissions into the atmosphere, ensure the integration of renewable energy sources into district heating and cooling systems, overcome the mismatch between production and demand and increase reliability and efficiency of entire systems. Such tanks operate on the principle of temperature stratification. In this paper, the processes of charging and discharging the heat storage tank used in district heating systems depending on the geometric and process parameters are analyzed and the thermal efficiency of each of these processes is calculated. The thermal efficiency of the tank charging process is calculated based on the distribution of the warmer water temperature in the tank after the complete tank charging process and varies between 53.85% and 96.75%. The thermal efficiency of the tank discharging process was calculated based on the warmer water outlet temperature and varies between 87.83% and 96.00%. Validation of mathematical model was achieved by comparing the data obtained by measuring the water temperature in the heat storage tank installed in the city thermal power plant‐heat plant and the results of numerical calculation.
Allometric conservatism in the evolution of bird beaks
Authors: Rombaut Louie M. K. , Capp Elliot J. R. , Cooney Christopher R. , Hughes Emma C. , Varley Zoë K. , Thomas Gavin H.
Published: December 2021

Evolution can involve periods of rapid divergent adaptation and expansion in the range of diversity, but evolution can also be relatively conservative over certain timescales due to functional, genetic-developmental, and ecological constraints. One way in which evolution may be conservative is in terms of allometry, the scaling relationship between the traits of organisms and body size. Here, we investigate patterns of allometric conservatism in the evolution of bird beaks with beak size and body size data for a representative sample of over 5000 extant bird species within a phylogenetic framework. We identify clades in which the allometric relationship between beak size and body size has remained relatively conserved across species over millions to tens of millions of years. We find that allometric conservatism is nonetheless punctuated by occasional shifts in the slopes and intercepts of allometric relationships. A steady accumulation of such shifts through time has given rise to the tremendous diversity of beak size relative to body size across birds today. Our findings are consistent with the Simpsonian vision of macroevolution, with evolutionary conservatism being the rule but with occasional shifts to new adaptive zones.
Ultrasound‐controlled drug release and drug activation for cancer therapy
Authors: Tu Li , Liao Zhihuan , Luo Zheng , Wu Yun‐Long , Herrmann Andreas , Huo Shuaidong
Published: December 2021

Traditional chemotherapy suffers from severe toxicity and side effects that limit its maximum application in cancer therapy. To overcome this challenge, an ideal treatment strategy would be to selectively control the release or regulate the activity of drugs to minimize the undesirable toxicity. Recently, ultrasound (US)‐responsive drug delivery systems (DDSs) have attracted significant attention due to the non‐invasiveness, high tissue penetration depth, and spatiotemporal controllability of US. Moreover, the US‐induced mechanical force has been proven to be a robust method to site‐selectively rearrange or cleave bonds in mechanochemistry. This review describes the US‐activated DDSs from the fundamental basics and aims to present a comprehensive summary of the current understanding of US‐responsive DDSs for controlled drug release and drug activation. First, we summarize the typical mechanisms for US‐responsive drug release and drug activation. Second, the main factors affecting the ultrasonic responsiveness of drug carriers are outlined. Furthermore, representative examples of US‐controlled drug release and drug activation are discussed, emphasizing their novelty and design principles. Finally, the challenges and an outlook on this promising therapeutic strategy are discussed.
Advanced bioactive nanomaterials for biomedical applications
Authors: Zhao Yu , Zhang Zhanzhan , Pan Zheng , Liu Yang
Published: December 2021

Bioactive materials are a kind of materials with unique bioactivities, which can change the cellular behaviors and elicit biological responses from living tissues. Bioactive materials came into the spotlight in the late 1960s when the researchers found that the materials such as bioglass could react with surrounding bone tissue for bone regeneration. In the following decades, advances in nanotechnology brought the new development opportunities to bioactive nanomaterials. Bioactive nanomaterials are not a simple miniaturization of macroscopic materials. They exhibit unique bioactivities due to their nanoscale size effect, high specific surface area, and precise nanostructure, which can significantly influence the interactions with biological systems. Nowadays, bioactive nanomaterials have represented an important and exciting area of research. Current and future applications ensure that bioactive nanomaterials have a high academic and clinical importance. This review summaries the recent advances in the field of bioactive nanomaterials, and evaluate the influence factors of bioactivities. Then, a range of bioactive nanomaterials and their potential biomedical applications are discussed. Furthermore, the limitations, challenges, and future opportunities of bioactive nanomaterials are also discussed.
Exploring new battery knowledge by advanced characterizing technologies
Authors: Wang Liguang , Liu Tiefeng , Wu Tianpin , Lu Jun
Published: December 2021

Exploration of science and technologies represents human's thirst for new knowledge and new life. Presently, we are in a stage of transferring the use of fossil fuels to renewable energy, which urgently calls for new energy materials and techniques beyond the boundary of human knowledge. On the way of scrutinizing these materials and surmounting the bottleneck of their performances, characterizing technologies are of critical importance in enabling the revealing of materials regarding their structural and chemical information, eventually establishing the correlations between microstructures and properties at the multiscale levels. Regrettably, traditional characterizations are hard to simultaneously probe electrochemistry with these chemical and physical structural evolutions, especially under operando conditions, or offer high‐resolution images of materials sensitive to electron‐beam irradiation. To this end, various advanced characterizing and diagnosing technologies recently developed, such as transmission X‐ray microscopy and cryo‐transmission electron microscopy, have demonstrated their benefits in understanding the energy storage behaviors of high‐performance energy materials (such as layered transition oxide cathode and Li metal anode). Benefited from new knowledge, the progress of high‐capacity electroactive materials is significantly accelerated. Here, we timely review the breakthroughs in emerging techniques and discuss how they guide the design of future battery materials to achieve the ultimate carbon neutrality.
Separation of tax service from audit service, going‐concern opinions, and discretionary accruals
Authors: Lai Kam‐Wah
Published: December 2021

This paper examines whether separating tax service of auditors from audit service improves audit quality. To some critics, the separation is the only solution to the independence problem created by the joint provision of both services by auditors. However, opponents argue that auditors are likely to have less client‐specific knowledge when they only provide audit service, resulting in lower audit quality. The results of this paper show that clients without the purchase of auditor‐provided tax service are more likely to have a going‐concern modified audit opinion and lower discretionary accruals than clients with such purchase. Additional tests indicate that clients with (without) auditor‐provided tax service would have had lower (higher) discretionary accruals or been more (less) likely to receive a going‐concern opinion had they had not (had) purchased the tax service. The results are robust to the control for possible self‐selection problem of clients’ purchase of tax service of auditors.
A tiny charge‐scaling in the OPLS‐AA + L‐OPLS force field delivers the realistic dynamics and structure of liquid primary alcohols
Authors: Zhang Xuan , Wang Yongtao , Yao Jia , Li Haoran , Mochizuki Kenji
Published: December 2021

We carry out molecular dynamics simulations for pure liquid primary alcohols ranging from methanol to 1‐decanol under ambient conditions. Based on the OPLS‐AA force field with the L‐OPLS correction, we demonstrate that a few % increases in the partial charges deliver the realistic dynamics (self‐diffusion coefficient and shear viscosity) and structure (density and X‐ray scattering intensity) as well as enthalpy of vaporization and isothermal compressibility. The validity against thermal expansion coefficient, isobaric heat capacity, and static dielectric constant are also discussed.
The bioactive compound carvacrol as a potential acaricide: An assessment of its effects on the integument of female Rhipicephalus sanguineus sensu lato ticks
Authors: Lima‐de‐Souza José Ribamar , de Oliveira Patrícia Rosa , Anholeto Luís Adriano , Sodelli Luís Fernando , Ferreira Allan Roberto Fernandes , Remedio Rafael Neodini , Camargo‐Mathias Maria Izabel
Published: December 2021

Studies seeking control methods for infestation of Riphicephalus sanguineus sensu lato (s.l.) ticks (dog ticks) have been carried out in order to minimize damage to both the tick's hosts and the environment, the latter due to the misuse of acaricide products. In this regard, carvacrol has been used as a natural alternative against ticks as it displays several properties including acaricidal. In this context, the present study aimed to evaluate the ultramorphology and morphohistochemistry of the integument of semi‐engorged R. sanguineus s.l. females exposed to different carvacrol concentrations. The findings indicate that the integument surface of females exposed to the highest carvacrol concentration (25 μl/ml) became wrinkled, suggesting dehydration or the result of integument cuticular and epithelial layer disorganization in response to the toxic product. Morphohistochemical integument layer alterations were more significant and intense in females exposed to the highest carvacrol concentration (25 μl/ml), confirming dose‐dependent carvacrol action. Among other cell and tissue alterations, changes in epithelial cell shape, size, and arrangement (epidermal layer) were noted, alongside altered and pyknotic‐shaped nuclei, suggesting a death process for these cells. This epithelium changed from simple cubic to stratified, also in response to the presence of the evaluated bioactive compound. Thus, the findings reported herein demonstrate that carvacrol may be an alternative for an efficient and more sustainable tick control in the near future.
Observation in inner ear of tree shrew using scanning electron microscope and the Atoh1 distribution in cochlea
Authors: He Jinling , Lu Shunlan , Mo Weijian , Tang Anzhou , Tan Songhua , Liu Lei , Fang Qin , Xie Lihong
Published: December 2021

This study aimed to observe the ultrastructure on the surface of the inner ear of a normal tree shrew using scanning electron microscope (SEM). The specimens of cochlea, macula utriculi, macula sacculi, and crista ampullaris of the normal adult tree shrew were collected and observed by SEM. We used immunofluorescence for cochlear protein Atoh1 staining. We observed that cochlea of the tree shrew is centered on the cochlear axis, circling about 3.5 times from bottom to top of the cochlea. The organ of Corti is located between medial and lateral grooves, including inner and outer hair cells as well as supporting cells. Maculae staticae include macula of saccule and macula of utricle, and the surface of macula is covered with a large number of otoliths. We found a gelatinous layer below the otoliths, followed by the layer of the honeycomb structure. The hair cell cilia of macula and crista ampullaris include one kinocilium and more stereocilia. There is no obvious cross structure but numerous hair cell cilia on semicircular canal crista ampullaris. Immunofluorescence staining showed that protein Atoh1 is mainly distributed in the nucleus of the cochlea's inner and outer hair cells. The observation of the inner ear structure under SEM elucidate the fine surface morphological structure of the entire cochlea, the vestibular maculae staticae, and crista ampullaris, providing new insight into the structure and function of the inner ear of tree shrew.

Highlights

This article is the first to describe the inner ear ultrastructure of a small primate tree shrew by scanning electron microscopy (SEM).

Under an SEM, the phalangeal processes of Deiter cells in tree shrews were observed to be connected to the tip of a neighboring hair cell, which was different from that of Deiters' cells in guinea pigs, and this crossed one hair cell, and connected to the tip of the third hair cell.

It was observed that the crista ampullaris of tree shrews were horseshoe‐shaped, and similar to that of humans and monkeys, this had no obvious “cross‐shaped hump” structure.

Tree shrew's ABR threshold value curve conforms to the mammalian U‐shaped curve, wave III is the main wave of ARB, its sensory frequency may be higher 8 kHz, and the characteristics of the stereocilia of tree shrew we have observed may be related to the perception of higher frequency hearing.
Ocean–atmosphere variability and drought in the insular Caribbean
Authors: Moraes Flávia D. S. , Mote Thomas L. , Seymour Lynne
Published: December 2021

The insular Caribbean experiences numerous climate and environmental hazards, including but not limited to hurricanes, floods, earthquakes, and drought. While some hazards are well explored in scientific literature, drought is considered one of the neglected hazards because of the lack of studies focusing on its causes and effects. This study identifies the spatial distribution of seasonal drought in insular Caribbean from 1950 to 2017, and its relationship with eastern Pacific (EP) and central Pacific (CP) ENSO, North Atlantic Oscillation (NAO), and Atlantic Meridional Mode (AMM). It brings a new perspective over the region by dividing the Caribbean into Greater Antilles and Bahamas (GA), and the Lesser Antilles (LA) to compare the role of those three teleconnection patterns on drought events over larger versus smaller islands. We used an existing high‐resolution drought atlas (4 km) based on monthly estimates of the self‐calibrating Palmer Drought Severity Index (scPDSI). Results indicate that there is a drying trend in all seasonal‐average scPDSI for both the GA and the LA, but more intense and frequent drought events occur in the LA. The LA is also the region with more widespread drought events, registering 12 years when the mid‐summer dry spell (MSD; July–August) had drought ≥80% of the area, while the GA registered only 2 years of MSD drought that extensive. The peak season AMM had the strongest positive correlation with GA and LA drought during April–November, while NAO was slightly stronger correlated with GA than with LA from July–November. For ENSO, CP El Niño years related stronger with drought in the LA from December–July, while the relationship between the two types of ENSO and the GA was not statistically significant. This effort aims to improve drought forecasts to help the region to better prepare for the prediction of seasonal droughts.
Nutrition practices and outcomes in patients with pediatric acute respiratory distress syndrome
Authors: Powell Matthew B. F. , Rajapreyar Prakadeshwari , Yan Ke , Sirinit Jitsupa , Mikhailov Theresa A.
Published: December 2021

Background

Pediatric acute respiratory distress syndrome (PARDS) remains a significant cause of morbidity and mortality. Evidence suggests enteral nutrition (EN) may be protective in critically ill children.

Methods

This is a retrospective cohort study comparing intubated patients with PARDS who received EEN and those who did not. We included patients aged 2 weeks to 18 years who could receive full nutrition enterally prior to their disease and excluded patients with cyanotic heart disease. Disease severity was captured with oxygenation index (OI), oxygen saturation index (OSI), and pediatric logistic organ dysfunction (PELOD‐2). EEN was defined as having received ≥25% of the calculated energy goal enterally within the first 48 h of PARDS diagnosis.

Results

We included 151 patients. Adjusted for age, OI, and OSI, the EEN group had a lower PICU mortality rate (adjusted odds ratio [aOR] = 0.071; 95% CI, 0.009–0.542; P = 0.011), had a higher likelihood of PICU discharge (adjusted risk ratio = 1.79; 95% CI, 1.25–2.55; P = 0.001), and was more likely to have at least one ventilator‐free day (aOR = 3.96; 95% CI, 1.28–12.22; P = 0.017). Adjusted for age and PELOD‐2, a statistically significant association between the EEN group and lower PICU mortality (P = 0.033), shorter PICU LOS (P < 0.001), and more ventilator‐free days (P = 0.037) persisted.

Conclusion

Our study found that EEN was associated with superior mortality rates, PICU LOS, and ventilator‐free days in patients with PARDS.
A reliable tool for detecting 7‐dehydrocholesterol and cholesterol in human plasma and its use in diagnosis of Smith–Lemli–Opitz syndrome
Authors: Luo Yitao , Liu Zhengyuan , Zeng Yujie , Zhang Yuxiao , Luan Yujing , Ma Li , Chen Li , Zou Lin , Yang Jingmin , Huang Zhibin , Rao Yulan , Zhang Chengqiang
Published: December 2021

Background

Smith–Lemli–Opitz syndrome is a birth defect caused by the deficiency of 7‐dehydrocholesterol reductase in cholesterol biosynthesis pathway, which leads to accumulation of 7‐dehydrocholesterol and reduction of cholesterol in body fluids. To effectively diagnose Smith–Lemli–Opitz syndrome and monitor therapy, a reliable method for simultaneous detection of 7‐dehydrocholesterol and cholesterol is needed.

Methods

In the presence of antioxidants (2,6‐ditert‐butyl‐4‐methylphenol and triphenylphosphine), 50 μL of human plasma were hydrolyzed at 70℃ for 40 min with 1 M potassium hydroxide in 90% ethanol, and then 7‐dehydrocholesterol and cholesterol were extracted by 600 μL of n‐hexane for three times. After microwave‐assisted derivatization with 70 μL of N,O‐bis(trimethylsilyl)trifluoroacetamide at 460 W for 3 min, the analytes were measured by gas chromatography‐mass spectrometry.

Results

The limits of detection were 100 ng/mL for 7‐dehydrocholesterol and 300 ng/mL for cholesterol. Good linearity was obtained in the range of 1–600 μg/mL for 7‐dehydrocholesterol and 10–600 μg/mL for cholesterol, which completely covered the biochemical levels of Smith–Lemli–Opitz syndrome patients that have been reported.

Conclusion

A time‐saving and accurate gas chromatography with mass spectrometry based method was developed for the determination of 7‐dehydrocholesterol and cholesterol in human plasma, which also serves as a useful tool for Smith–Lemli–Opitz syndrome diagnosis, treatment, and research.
Hydrated Hydroxide Complex Dominates the AIE Properties of Nonconjugated Polymeric Luminophores
Authors: Yang Taiqun , Zhou Jiafeng , Shan Bingqian , Li Lei , Zhu Chun , Ma Chaoqun , Gao Hui , Chen Guoqing , Zhang Kun , Wu Peng
Published: December 2021

Nontraditional intrinsic luminescence (NTIL) which always accompanied with aggregation‐induced emission (AIE) features has received considerable attention due to their importance in the understanding of basic luminescence principle and potential practical applications. However, the rational modulation of the NTIL of nonconventional luminophores remains difficult, on account of the limited understanding of emission mechanisms. Herein, the emission color of nonconjugated poly(methyl vinyl ether‐alt‐maleic anhydride) (PMVEMA) can be readily regulated from blue to red by controlling the alkalinity during the hydrolysis process. The nontraditional photoluminescence with AIE property is from the new formed p‐band state, resulting from the strong overlapping of p orbitals of the clustered O atoms through space interactions. Hydrated hydroxide complexes embedded in the entangled polymer chain make big difference on the clustering of O atoms which dominates the AIE property of nonconjugated PMVEMA. These new insights into the photoluminescence mechanism of NTIL should stimulate additional experimental and theoretical studies and can benefit the molecular‐level design of nontraditional chromophores for optoelectronics and other applications.
Silent variant in F8:c.222G>T (p.Thr74Thr) causes a partial exon skipping in a patient with mild hemophilia A
Authors: Letelier Anna , Ljung Rolf , Olsson Anna , Andersson Nadine G.
Published: December 2021

One of the challenges of genetic testing in patients with hemophilia A is the interpretation of sequence variants. Here we report a silent variant found in exon 2 in the F8 gene in a 47‐year‐old patient with a previous von Willebrand disease (VWD) type 1 diagnosis. Clinically he had mild bleeding symptoms restricted to prolonged bleeding from minor wounds. Sanger sequencing of F8 gene using genomic DNA showed a hemizygous silent variant in exon 2: c.222G>T, p.Thr74Thr. When applying ACMG criteria, the variant was predicted to be “likely benign” in the analyzing software or VUS after curating. Sanger sequencing of the patient's cDNA after nested polymerase chain reaction showed that the patient had both a normal transcript containing exons 1–4 and a defect transcript lacking exon 2. These findings explain the patient's low FVIII:C level and led to the diagnosis of mild hemophilia A instead of VWD type 1. This case illustrates that mRNA work‐up may be needed to clarify a patient's phenotype–genotype.
Global existence and decay of solutions for a system of viscoelastic wave equations of Kirchhoff type with logarithmic nonlinearity
Authors: Irkıl Nazlı , Pişkin Erhan , Agarwal Praveen
Published: December 2021

This work deals with a system of Kirchhoff‐type equations with viscoelastic term and logarithmic nonlinearity. First, we proved the global existence by combining the potential well method with Faedo–Galerkin's procedure. Later, we established decay rate estimates by using multiplier method.
Modeling the transmission of second‐wave COVID‐19 caused by imported cases: A case study
Authors: Guo Youming , Li Tingting
Published: December 2021

As the first‐wave COVID‐19 has passed in 2020, people's awareness of self‐protection began to decline gradually. How to prevent and control the second‐wave COVID‐19 has become an important issue in many countries and regions. By analyzing the transmission of the second‐wave COVID‐19 caused by an imported case in Tonghua City, Jilin Province, China, in January 2021, we establish a new mathematical COVID‐19 model to simulate the transmission characteristics of the second‐wave COVID‐19. First, we analyze the basic properties of the model, prove the existence of the equilibrium point, and obtain the expression of the basic reproduction number with important biological significance. Secondly, we use the weighted nonlinear least square estimation method to fit the cases in Tonghua City of Jilin Province in January 2021, and get the estimated value of the parameters. The basic reproduction number of the second‐wave COVID‐19 in Tonghua City is , which is much smaller than that of the first‐wave COVID‐19 in Wuhan in 2020. Finally, in the optimal control part, we consider two control methods (keeping social distance and nucleic acid detection of all people in the city) to simulate the control of the disease. The results show that the control intensity of the two control methods needs to be dynamically changed and adjusted, so that the cost can be minimized with the least infection. The results of this paper can not only provide suggestions for health management departments, but also provide a reference for the analysis of the second‐wave COVID‐19 in other countries or regions.
On the stability of hydrostatic equilibrium in a uniform magnetic field with partial dissipation
Authors: Ji Xintong , Bian Dongfen
Published: December 2021

In this paper, we establish the nonlinear stability and large time behavior of hydrostatic equilibrium in a uniform magnetic field for the 2D Boussinesq system with magnetohydrodynamics convection on spatial domain
with partial dissipation. This is the important part of further work about the stability/instability of shear flow which is the combination of hydrostatic equilibrium and Couette/shear flow in a uniform magnetic field with partial dissipation.
Comment on “Bipolar fuzzy relation equations systems based on the product t‐norm”
Authors: YongBin OuYang
Published: December 2021

This note provides counterexamples to illustrate that Theorem 4 which is proposed by Cornejo, Lobo, and Medina (Bipolar fuzzy relation equations systems based on the product t‐norm. Mathematical Methods in the Applied Sciences. 2019,42(17):5779‐5793) is incorrect. The incorrect of Theorem 4 is due to the inaccuracy of the definition of feasible pair. Then, we present the correction of the definition of feasible pair to the contention.
Nuclear magnetic resonance/magnetic resonance imaging on lubricating greases: Observation of bleeding and aging
Authors: Rudszuck Thomas , Schork Nicolas , Nirschl Hermann , Guthausen Gisela
Published: December 2021

Lubricating greases were investigated by nuclear magnetic resonance/magnetic resonance imaging (NMR/MRI) to get insight into their structure and into their response to mechanical forces, which is related to bleeding and aging. The investigated greases are based on metallic soaps of fatty acids and oils, whereby LiOH is often used. These organic soaps act as thickeners and provide a network in which oils and their additives are embedded. Lubricating greases can thus be considered as a class of substances similar to oleogels or even hydrogels. Questions arise about translational mobility of guest molecules, mainly base oil, in these networks. Molecular structuring and interactions within the network of thickeners are of interest as they are related to macroscopic stability. Apart from NMR spectroscopy (1H‐,7Li‐ and31P‐NMR), spectrally resolved relaxation and diffusion measurements are used for characterization. In addition, magic angle spinning (MAS)‐NMR was combined with1H‐MRI to investigate the impact of mechanical stress and swelling of lubricating greases.
Improving Latex‐Based Pressure‐Sensitive Adhesive Properties Using Carboxylated Cellulose Nanocrystals
Authors: Gabriel Vida A. , Tousignant Mathieu N. , Wilson Sean M.W. , Faure Marie D.M. , Cranston Emily D. , Cunningham Michael F. , Lessard Benoît H. , Dubé Marc A.
Published: December 2021

Cellulose nanocrystals (CNCs) are becoming a popular option when producing polymer nanocomposites because they are a green alternative to petroleum‐based performance enhancers and provide significant matrix reinforcement at low loadings. DextraCel is a commercial grade CNC with carboxylate surface groups that can be dispersed in water without sonication. These carboxylated CNCs (cCNCs) can be incorporated in situ via seeded semi‐batch emulsion polymerization to produce latexes for adhesive applications. The resulting nanocomposite films exhibit 26x higher peel strength, 4.5x higher tack, and 7.7x higher shear strength relative to base case films. Curiously, adhesives produced from latexes containing cCNCs that do not undergo ultrasonication display greater adhesive property improvements relative to films produced with cCNCs that are ultrasonicated. Atomic force microscopy images reveal that cCNCs have stronger self interactions than their sulfated CNCs counterparts; cCNCs display side‐by‐side and end‐to‐end association in films when they are not ultrasonicated, which increases their “apparent” aspect ratio—an important characteristic attributed to matrix reinforcement. Omitting ultrasonication preserves cCNC‐cCNC interactions that cause them to behave like nanofibers rather than discrete nanocrystals; this allows them to display greater mechanical enhancements, similar to reinforcements provided by nanofibrils, without the technical challenges associated with producing composite latexes with nanofibrils.
External validation of Solomon–Greenwell nomogram for female bladder outlet obstruction
Authors: Mai Hsing‐Chia , Wu Richard C. , Lin Victor C. , Kuo Wade W.‐T. , Wu Chun‐Hsien
Published: December 2021

Aim

There is no unified diagnostic standard for female bladder outlet obstruction (BOO) to date. The Solomon–Greenwell (S–G) nomogram was developed to indicate the probability of female BOO by performing a pressure‐flow study, and the equation of the BOO Index in females (BOOIf) is PdetQmax − 2.2 × Qmax. We aimed to validate the diagnostic value of the S–G nomogram in female BOO.

Materials and Methods

We retrospectively reviewed a videourodynamic study (VUDS) cohort in our institution. Between 2015 and 2020, 192 female patients underwent VUDS for lower urinary tract dysfunction (LUTD). We excluded patients with neurogenic LUTD (n = 30) and patients with no detrusor contraction and/or no void during VUDS (n = 51). The diagnosis of female BOO was based on the Nitti criteria (radiological evidence of urethral narrowing in the presence of a sustained detrusor pressure). BOOIf was calculated for each enrolled patient. The cutoff values of BOOIf were set at <0, >5, and >18 as the original S–G nomogram proposed. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each threshold to diagnose female BOO were calculated.

Results

Out of the 111 enrolled patients, 43 (38.7%) were diagnosed as having female BOO by VUDS. The most common etiology of female BOO was dysfunctional voiding (19/43, 44.2%), followed by primary bladder neck obstruction (PBNO, 15/43, 34.9%). When the cutoff value was <0 (low probability of obstruction), the sensitivity, specificity, PPV, and NPV were 90%, 91%, 92%, and 87%, respectively; when >5 (likely obstructed), the values were 79%, 96%, 92%, and 88%, respectively; and when >18 (obstruction almost certain), the values were 47%, 100%, 100%, and 75%, respectively. Fourteen of 15 PBNO patients would be classified as non‐BOO if the cutoff value was >18. Six PBNO patients would not be diagnosed as female BOO if the threshold was >5.

Conclusion

A BOOIf <0 showed good diagnostic value for excluding female BOO. A BOOIf >18 had perfect specificity and PPV for diagnosing female BOO. However, the sensitivity of the S–G nomogram for detecting female BOO was unsatisfactory, especially for patients with PBNO. VUDS remains the examination of choice for patients with suspected female BOO.