bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computer‐assisted planning with 3D printing for mandibular reconstruction caused by a mandibular fracture with secondary osteomyelitis: A Case Report
Authors: Barreda Hale Mauricio , Romero‐Araya Pablo , Cea Herrera Macarena , Espinoza Daniela , Castro Nicolas , Castro Joaquín , Serandour Guillaume 
Published: July 2021

AbstractMandibular reconstructions are complex clinical pictures that require careful planning for functional and aesthetic outcomes. Virtual surgical planning and 3D printing are ideal to achieve a predictable result. Through “hybrid techniques” (prebending plates with 3D‐models) and free software, this goal is within reach for clinics with limited financial resources.
Electroless Plating of Metal Nanomaterials
Authors: Muench Falk 
Published: July 2021

AbstractInvited for this month's cover picture is Falk Muench. The cover picture shows electrolessly plated nanostructures from the author′s research, clockwise and starting from the top: silver nanoparticles on glass, employed in plasmonic biosensing. Copper‐platinum nanotubes, fabricated to demonstrate the nanoscale conformality of the alloy plating reaction. Silver nanoplates, which spontaneously form during kinetically controlled, anisotropic growth. Stacked layers of porous silver nanosheets, which represent a dendritic version of the previous nanoplates. Read the full text of the Review at 10.1002/celc.202100285.
Advances in carbon‐based thermoelectric materials for high‐performance, flexible thermoelectric devices
Authors: Yun Jeong‐Seob , Choi Seongyun , Im Sang Hyuk 
Published: July 2021

AbstractWaste energy harvesting can contribute to the increase of the efficiency of many industrial processes, which consume energy to produce valuable products. Among all the wasted energy, heat energy is the most abundant, existing in almost any situation. Thermoelectric devices have the capability to harvest and convert the thermal energy into electrical power via the Seebeck effect. With its simple operating principle, thermoelectric devices can be reliable even under the harshest environments, taking advantage of any type of heat source. As a result, various inorganic and organic materials are being explored as thermoelectric materials. Among the reported materials, carbon‐based materials are promising in terms of commericialization, due to their nontoxic and abundant nature, and solution processability. In particular, poly(3,4‐ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS), carbon nanotubes, and graphene are extensively studied as thermoelectric materials owing to their remarkable thermoelectric performance. Also, organic–inorganic hybrid halide perovskites show the potential to be used as future high‐performance thermoelectric materials. Here, the progess in carbon materials as thermoelectrics is reviewed in detail, focusing on four base materials (PEDOT:PSS, carbon nanotubes, graphene, and organic–inorganic hybrid halide perovskites). This review illuminates the potential of carbon‐based materials in the field of thermoelectrics and their application to next‐generation energy devices.
Identification of a Putative β‐Arrestin Superagonist of the Growth Hormone Secretagogue Receptor (GHSR)
Authors: Karaki Fumika , Oki Tomoya , Sakao Yuma , Sato Noriko , Hirayama Shigeto , Miyano Kanako , Uezono Yasuhito , Fujii Hideaki 
Published: July 2021

AbstractGhrelin is a pleiotropic feeding hormone which also has a pivotal role in the central nervous system. Upon the activation of its receptor, growth hormone secretagogue receptor (GHSR), the Gαq/11‐mediated and the β‐arrestin‐mediated signaling pathways are activated. As the β‐arrestin pathway is a potential drug target, there is a strong need for β‐arrestin‐biased GHSR modulators. Activation of the β‐arrestin pathway should inhibit the Gαq/11‐mediated calcium flux through internalization of the receptor. Hence, we used the antagonistic activity in the calcium assay as the first screening for the β‐arrestin activation. By conducting the second screening assay for the β‐arrestin activation based on extracellular signal regulated kinase (ERK) 1/2 phosphorylation, we discovered a putative β‐arrestin‐biased superagonist. The activity of the compound was not completely blocked with the competitive antagonist, which implies that the effect is mediated, at least partly, by allosteric binding of the compound.
Calcification‐Based Cancer Diagnosis and Therapy
Authors: Shou Hao , Wu Jicheng , Tang Ning , Wang Ben 
Published: July 2021

AbstractIn nature, calcium deposition is a common biological process in mammals that shapes mechanical structures and creates the functions of bones and teeth, and causes calculi formation. Spontaneous tumor calcification and regional lymph node calcification in colorectal cancer, lung cancer, and glioblastoma have been proven to be benign prognostic factors in the clinic. In line with this concept, we introduce the idea and lead the compound development of artificially inducing bionic calcification around the surface of cancer cells. This process is shown to have excellent effects in the inhibition of growth and metastases of cervical, breast, and lung tumors, as well as superb performance in early‐stage diagnosis. Therefore, we predict that this concept may open the door for cancer targeting calcification therapy and diagnosis and provide an outlook for a new avenue in anticancer drug development.
Microscale Parallel Synthesis of Acylated Aminotriazoles Enabling the Development of Factor XIIa and Thrombin Inhibitors
Authors: Platte Simon , Korff Marvin , Imberg Lukas , Balicioglu Ilker , Erbacher Catharina , Will Jonas M. , Daniliuc Constantin G. , Karst Uwe , Kalinin Dmitrii V. 
Published: July 2021

AbstractHerein we report a microscale parallel synthetic approach allowing for rapid access to libraries of N‐acylated aminotriazoles and screening of their inhibitory activity against factor XIIa (FXIIa) and thrombin, which are targets for antithrombotic drugs. This approach, in combination with post‐screening structure optimization, yielded a potent 7 nM inhibitor of FXIIa and a 25 nM thrombin inhibitor; both compounds showed no inhibition of the other tested serine proteases. Selected N‐acylated aminotriazoles exhibited anticoagulant properties in vitro influencing the intrinsic blood coagulation pathway, but not extrinsic coagulation. Mechanistic studies of FXIIa inhibition suggested that synthesized N‐acylated aminotriazoles are covalent inhibitors of FXIIa. These synthesized compounds may serve as a promising starting point for the development of novel antithrombotic drugs.
Clinical and genetic risk factors for radiation‐associated ototoxicity: A report from the Childhood Cancer Survivor Study and the St. Jude Lifetime Cohort
Authors: Trendowski Matthew R. , Baedke Jessica L. , Sapkota Yadav , Travis Lois B. , Zhang Xindi , El Charif Omar , Wheeler Heather E. , Leisenring Wendy M. , Robison Leslie L. , Hudson Melissa M. , Morton Lindsay M. , Oeffinger Kevin C. , Howell Rebecca M. , Armstrong Gregory T. , Bhatia Smita , Dolan M. Eileen 
Published: July 2021

BACKGROUNDCranial radiation therapy (CRT) is associated with ototoxicity, which manifests as hearing loss and tinnitus. The authors sought to identify clinical determinants and genetic risk factors for ototoxicity among adult survivors of pediatric cancer treated with CRT.METHODSLogistic regression evaluated associations of tinnitus (n = 1991) and hearing loss (n = 2198) with nongenetic risk factors and comorbidities among CRT‐treated survivors in the Childhood Cancer Survivor Study. Genome‐wide association studies (GWASs) of CRT‐related tinnitus and hearing loss were also performed.RESULTSMales were more likely to report CRT‐related tinnitus (9.4% vs 5.4%; P = 5.1 × 10−4) and hearing loss (14.0% vs 10.7%; P = .02) than females. Survivors with tinnitus or hearing loss were more likely to experience persistent dizziness or vertigo (tinnitus: P < 2 × 10−16; hearing loss: P = 6.4 × 10−9), take antidepressants (tinnitus: P = .02; hearing loss: P = .01), and report poorer overall health (tinnitus: P = 1.5 × 10−6; hearing loss: P = 1.7 × 10−6) in comparison with controls. GWAS of CRT‐related tinnitus revealed a genome‐wide significant signal in chromosome 1 led by rs203248 (P = 1.5 × 10−9), whereas GWAS of CRT‐related hearing loss identified rs332013 (P = 5.8 × 10−7) in chromosome 8 and rs67522722 (P = 7.8 × 10−7) in chromosome 6 as nearly genome‐wide significant. A replication analysis identified rs67522722, intronic to ATXN1, as being significantly associated with CRT‐related hearing loss (P = .03) and de novo hearing loss (P = 3.6 × 10−4).CONCLUSIONSCRT‐associated ototoxicity was associated with sex, several neuro‐otological symptoms, increased antidepressant use, and poorer self‐reported health. GWAS of CRT‐related hearing loss identified rs67522722, which was supported in an independent cohort of survivors.LAY SUMMARY

Hearing loss and subjective tinnitus (the perception of noise or ringing in the ear) are long‐term side effects of cancer treatment and are common in children treated with radiation to the brain.

These toxicities can affect childhood development and potentially contribute to serious learning and behavioral difficulties.

This study's data indicate that males are at greater risk for hearing loss and tinnitus than females after radiation therapy to the brain.

Those who develop these toxicities are more likely to use antidepressants and report poorer overall health.

Health care providers can improve the management of survivors by informing patients and/or their parents of these risks.
Pharmacokinetics and Bioequivalence of a Generic Fixed‐Dose Combination Tablet of Metformin Hydrochloride/Vildagliptin Versus a Branded Product in Healthy Chinese Subjects Under Fed and Fasting Conditions
Authors: Ye LiJun , Li Bei , Ling NengMing , Gao Yue , Tao XueXia , Cai ShuFan , Wang Yan , Chen ShaoChun , Wang Fei 
Published: July 2021

AbstractThe purpose of this study was to compare the bioequivalence and safety of test and reference preparations of fixed‐dose combination tablets of metformin hydrochloride/vildagliptin 850 mg/50 mg in healthy volunteers under fasting and fed conditions for marketing authorization in China. A single‐dose, randomized, open‐label, 2‐way crossover study was conducted. Blood samples were collected up to 36 hours after dosing in each period with a 7‐day washout. Pharmacokinetic parameters, including maximum plasma concentration (Cmax), time to reach Cmax, area under the plasma concentration–time curve (AUC) from time 0 to the last time point of the measurable concentration, AUC from time 0 to infinity, terminal elimination half‐life, and apparent clearance, were calculated using noncompartmental methods and compared between the 2 formulations. Safety profiles were assessed, including significant findings of vital signs, electrocardiogram, laboratory tests, physical examination, and adverse events. A total of 30 healthy subjects (19 men, 11 women) were randomized, and 29 subjects were treated under fasting conditions. Likewise, 30 subjects (24 men, 6 women) were randomized and treated under fed conditions. The geometric mean ratio and corresponding 90% confidence intervals of Cmax, AUC from time 0 to the last time point of the measurable concentration , and AUC from time 0 to infinity for both metformin hydrochloride and vildagliptin between the 2 fixed‐dose combination formulations were within the bioequivalence acceptance range of 80% to 125% under fasting or fed conditions. Therefore, the generic and branded formulations were bioequivalent and well tolerated in healthy Chinese subjects.
Methadone Destabilizes Cardiac Repolarization During Sleep
Authors: Solhjoo Soroosh , Punjabi Naresh M. , Ivanescu Andrada E. , Crainiceanu Ciprian , Gaynanova Irina , Wicken Cassie , Buckenmaier Chester , Haigney Mark C. 
Published: July 2021

Methadone, a widely prescribed medication for chronic pain and opioid addiction, is associated with respiratory depression and increased predisposition for torsades de pointes, a potentially fatal arrhythmia. Most methadone‐related deaths occur during sleep. The objective of this study was to determine whether methadone’s arrhythmogenic effects increase during sleep, with a focus on cardiac repolarization instability using QT variability index (QTVI), a measure shown to predict arrhythmias and mortality. Sleep study data of 24 patients on chronic methadone therapy referred to a tertiary clinic for overnight polysomnography were compared with two matched groups not on methadone: 24 patients referred for overnight polysomnography to the same clinic (clinic group), and 24 volunteers who had overnight polysomnography at home (community group). Despite similar values for heart rate, heart rate variability, corrected QT interval, QTVI, and oxygen saturation (SpO2) when awake, patients on methadone had larger QTVI (P = 0.015 vs. clinic, P < 0.001 vs. community) and lower SpO2 (P = 0.008 vs. clinic, P = 0.013 vs. community) during sleep, and the increase in their QTVI during sleep vs. wakefulness correlated with the decrease in SpO2 (r = −0.54, P = 0.013). QTVI positively correlated with methadone dose during sleep (r = 0.51, P = 0.012) and wakefulness (r = 0.73, P < 0.001). High‐density ectopy (> 1,000 premature beats per median sleep period), a precursor for torsades de pointes, was uncommon but more frequent in patients on methadone (P = 0.039). This study demonstrates that chronic methadone use is associated with increased cardiac repolarization instability. Methadone’s pro‐arrhythmic impact may be mediated by sleep‐related hypoxemia, which could explain the increased nocturnal mortality associated with this opioid.
Long noncoding RNA IL6‐AS1 is highly expressed in chronic obstructive pulmonary disease and is associated with interleukin 6 by targeting miR‐149‐5p and early B‐cell factor 1
Authors: Yi Erkang , Zhang Jiahuan , Zheng Mengning , Zhang Yi , Liang Chunxiao , Hao Binwei , Hong Wei , Lin Biting , Pu Jinding , Lin Zhiwei , Huang Peiyu , Li Bing , Zhou Yumin , Ran Pixin 
Published: July 2021

AbstractChronic obstructive pulmonary disease is a complex condition with multiple etiologies, including inflammation. We identified a novel long noncoding RNA (lncRNA), interleukin 6 antisense RNA 1 (IL6‐AS1), which is upregulated in this disease and is associated with airway inflammation. We found that IL6‐AS1 promotes the expression of inflammatory factors, especially interleukin (IL) 6. Mechanistically, cytoplasmic IL6‐AS1 acts as an endogenous sponge by competitively binding to the microRNA miR‐149‐5p to stabilize IL‐6 mRNA. Nuclear IL6‐AS1 promotes IL‐6 transcription by recruiting early B‐cell factor 1 to the IL‐6 promoter, which increases the methylation of the H3K4 histone and acetylation of the H3K27 histone. We propose a model of lncRNA expression in both the nucleus and cytoplasm that exerts similar effects through differing mechanisms, and IL6‐AS1 probably increases inflammation via multiple pathways.
Increase in sexual motivation throughout adolescence in the cycling female rat
Authors: Armas Magdalena , Marín Gabriella , Uriarte Natalia , Agrati Daniella 
Published: July 2021

AbstractSexual behavior in the female rat is a highly motivated behavior first displayed during adolescence, a developmental period when neural circuits underlying motivation are not mature. This study characterizes the natural development of sexual motivation and behavior of female rats. We compared the incentive value of the male for mid‐adolescent (PNDs:39‐43), late adolescent (PNDs:49‐53), and adult (PNDs:90‐115) cycling females, using a male–female preference task and an ultrasonic vocalization emission test following exposure to a male or female stimulus animal. Furthermore, display of sexual and social behaviors during an interaction with a male or a nonreceptive female was assessed. Mid‐adolescent rats exhibited a reduced preference for the male than adults and performed less attempts to access the male. Unlike late adolescent and adult females, mid‐adolescent rats did not increase their ultrasonic vocalization emission after interacting with a male relative to a female. Although most of the sexual behavior did not differ between groups, mid‐adolescent females showed lower lordosis magnitude and higher levels of play and social investigation during a sexual interaction, giving rise to a unique behavioral profile. Present results indicate that the sexual behavior repertoire is fully displayed by mid‐adolescence, but sexual motivation is low and increases into late adolescence.
Unconventional translation initiation factor EIF2A is required for Drosophila spermatogenesis
Authors: Lowe David D. , Montell Denise J. 
Published: July 2021

AbstractBackgroundEIF2A is an unconventional translation factor required for initiation of protein synthesis from non‐AUG codons from a variety of transcripts, including oncogenes and stress related transcripts in mammalian cells. Its function in multicellular organisms has not been reported.ResultsHere, we identify and characterize mutant alleles of the CG7414 gene, which encodes the Drosophila EIF2A ortholog. We identified that CG7414 undergoes sex‐specific splicing that regulates its male‐specific expression. We characterized a Mi{Mic} transposon insertion that disrupts the coding regions of all predicted isoforms and is a likely null allele, and a PBac transposon insertion into an intron, which is a hypomorph. The Mi{Mic} allele is homozygous lethal, while the viable progeny from the hypomorphic PiggyBac allele are male sterile and female fertile. In dEIF2A mutant flies, sperm failed to individualize due to defects in F‐actin cones and failure to form and maintain cystic bulges, ultimately leading to sterility.ConclusionsThese results demonstrate that EIF2A is essential in a multicellular organism, both for normal development and spermatogenesis, and provide an entrée into the elucidation of the role of EIF2A and unconventional translation in vivo.
A recovery network leads to the natural recolonization of an archipelago and a potential trailing edge refuge
Authors: Smith Matthew M. , Gilbert Jonathan H. , Olson Erik R. , Scribner Kim T. , Van Deelen Timothy R. , Van Stappen Julie F. , Williams Bronwyn W. , Woodford James E. , Pauli Jonathan N. 
Published: July 2021

AbstractRapid environmental change is reshaping ecosystems and driving species loss globally. Carnivore populations have declined and retracted rapidly and have been the target of numerous translocation projects. Success, however, is complicated when these efforts occur in novel ecosystems. Identifying refuges, locations that are resistant to environmental change, within a translocation framework should improve population recovery and persistence. American martens (Martes americana) are the most frequently translocated carnivore in North America. As elsewhere, martens were extirpated across much of the Great Lakes region by the 1930s and, despite multiple translocations beginning in the 1950s, martens remain of regional conservation concern. Surprisingly, martens were rediscovered in 2014 on the Apostle Islands of Lake Superior after a putative absence of >40 yr. To identify the source of martens to the islands and understand connectivity of the reintroduction network, we collected genetic data on martens from the archipelago and from all regional reintroduction sites. In total, we genotyped 483 individual martens, 43 of which inhabited the Apostle Islands (densities 0.42–1.46 km−2). Coalescent analyses supported the contemporary recolonization of the Apostle Islands with progenitors likely originating from Michigan, which were sourced from Ontario. We also identified movements by a first‐order relative between the Apostle Islands and the recovery network. We detected some regional gene flow, but in an unexpected direction: individuals moving from the islands to the mainland. Our findings suggest that the Apostle Islands were naturally recolonized by progeny of translocated individuals and now act as a source back to the reintroduction sites on the mainland. We suggest that the Apostle Islands, given its protection from disturbance, complex forest structure, and reduced carnivore competition, will act as a potential refuge for marten along their trailing range boundary and a central node for regional recovery. Our work reveals that translocations, even those occurring along southern range boundaries, can create recovery networks that function like natural metapopulations. Identifying refuges, locations that are resistant to environmental change, within these recovery networks can further improve species recovery, even within novel environments. Future translocation planning should a priori identify potential refuges and sources to improve short‐term recovery and long‐term persistence.
Disturbance‐accelerated succession increases the production of a temperate forest
Authors: Gough Christopher M. , Bohrer Gil , Hardiman Brady S. , Nave Lucas E. , Vogel Christoph S. , Atkins Jeff W. , Bond‐Lamberty Ben , Fahey Robert T. , Fotis Alexander T. , Grigri Maxim S. , Haber Lisa T. , Ju Yang , Kleinke Callie L. , Mathes Kayla C. , Nadelhoffer Knute J. , Stuart‐Haëntjens Ellen , Curtis Peter S. 
Published: July 2021

AbstractMany secondary deciduous forests of eastern North America are approaching a transition in which mature early‐successional trees are declining, resulting in an uncertain future for this century‐long carbon (C) sink. We initiated the Forest Accelerated Succession Experiment (FASET) at the University of Michigan Biological Station to examine the patterns and mechanisms underlying forest C cycling following the stem girdling‐induced mortality of >6,700 early‐successionalPopulusspp. (aspen) andBetula papyrifera(paper birch). Meteorological flux tower‐based C cycling observations from the 33‐ha treatment forest have been paired with those from a nearby unmanipulated forest since 2008. Following over a decade of observations, we revisit our core hypothesis: that net ecosystem production (NEP) would increase following the transition to mid‐late‐successional species dominance due to increased canopy structural complexity. Supporting our hypothesis, NEP was stable, briefly declined, and then increased relative to the control in the decade following disturbance; however, increasing NEP was not associated with rising structural complexity but rather with a rapid 1‐yr recovery of total leaf area index as mid‐late‐successionalAcer,Quercus, andPinusassumed canopy dominance. The transition to mid‐late‐successional species dominance improved carbon‐use efficiency (CUE = NEP/gross primary production) as ecosystem respiration declined. Similar soil respiration rates in control and treatment forests, along with species differences in leaf physiology and the rising relative growth rates of mid‐late‐successional species in the treatment forest, suggest changes in aboveground plant respiration and growth were primarily responsible for increases in NEP. We conclude that deciduous forests transitioning from early to middle succession are capable of sustained or increased NEP, even when experiencing extensive tree mortality. This adds to mounting evidence that aging deciduous forests in the region will function as C sinks for decades to come.