bluuebunny/crossref_metadata_2025 huggingface dataset:
Upregulation of IL‐8, osteonectin, and myonectin mRNAs by intermittent hypoxia via OCT1‐ and NRF2‐mediated mechanisms in skeletal muscle cells
Authors: Takasawa Shin , Shobatake Ryogo , Itaya‐Hironaka Asako , Makino Mai , Uchiyama Tomoko , Sakuramoto‐Tsuchida Sumiyo , Takeda Yoshinori , Ota Hiroyo , Yamauchi Akiyo
Published: December 2022

Sleep apnoea syndrome is characterized by recurrent episodes of oxygen desaturation and reoxygenation (intermittent hypoxia [IH]) and is a risk factor for insulin resistance/Type 2 diabetes. The induction of insulin resistance in skeletal muscle is a key phenomenon to develop diabetes. However, the mechanisms linking IH stress and insulin resistance remain elusive. We exposed human RD and mouse C2C12 muscle cells to normoxia or IH and measured their mRNA levels by real‐time RT‐PCR. We found that IH significantly increased the mRNA and protein levels of muscle‐derived insulin resistance‐factors (myokines) such as IL‐8, osteonectin (ON), and myonectin (MN) in muscle cells. We further analysed the IH‐induced expression mechanisms of IL‐8, ON, and MN genes in muscle cells. Deletion analyses of the human myokine promoter(s) revealed that the regions −152 to −151 in IL‐8, −105 to −99 in ON, and − 3741 to −3738 in MN promoters were responsible for the activation by IH in RD cells. The promoters contain consensus transcription factor binding sequences for OCT1 in IL‐8 and MN promoters, and for NRF2 in ON promoter, respectively. The introduction of siRNA for OCT1 abolished the IH‐induced expression(s) of IL‐8 and MN and siRNA for NRF2 abolished the IH‐induced expression of ON.
Pontine lesion in hyperglycemic crises: Relevance to osmotic demyelination syndrome and posterior reversible encephalopathy syndrome
Authors: Murao Satoshi , Kiuchi Takaaki , Hasegawa Momoka , Yoshikawa Ritsuko
Published: December 2022

We herein describe a case of type 1 diabetes that presented with a pontine lesion during two hyperglycemic crises accompanied by marked fluctuations in serum osmotic pressure and blood pressure. Magnetic resonance imaging showed swollen pons with osmotic demyelination syndrome characteristics accompanying cytotoxic edema at the first crisis. The involvement of vasogenic edema was also assumed in the second crisis. Neurological symptoms were milder than magnetic resonance imaging findings. The patient recovered after 7 days without sequelae in both crises. Based on these findings, a pontine lesion needs to be considered in patients with poorly controlled diabetes showing rapid metabolic and blood pressure changes, as observed in hyperglycemic crises. Cytotoxic edema leading to osmotic demyelination syndrome and vasogenic edema caused by vascular endothelial cell damage might both be involved in the pathogenesis of a pontine lesion.
XX/XY sex chromosomes in a blind lizard (Dibamidae): Towards understanding the evolution of sex determination in squamates
Authors: Rovatsos Michail , Galoyan Eduard , Spangenberg Victor , Vassilieva Anna , Kratochvíl Lukáš
Published: December 2022

The reconstruction of the evolutionary history of sex determination in squamate reptiles (lizards and snakes) is complicated by missing data in many lineages, erroneous reports, and often questionable inferences on state homology. Therefore, despite the large effort, the reconstruction of the ancestral sex determination in squamate reptiles is still controversial. With the hope to shed light on this problem, we aspired to identify the sex chromosome gene content in Dibamus deharvengi, the representative of the family Dibamidae, the putative sister clade to all other squamates. Our analyses revealed XX/XY sex‐determination system in D. deharvengi: the X chromosome contains genes with homologues scattered across chicken chromosomes 8, 12, 13, 18, 30, and 33, and the Y chromosome seems to largely degenerate. To the best of our knowledge, this combination has never been reported to form sex chromosomes in any amniote lineage. It suggests that the sex chromosomes can represent an apomorphy of a clade including D. deharvengi. Our findings cover an important gap in the knowledge of sex determination in reptiles and further support multiple independent origins of sex chromosomes in this group.
A bibliometric and visualized analysis of liver fibrosis from 2002 to 2022
Authors: Zhao Qianqian , Liang Luhua , Zhai Fei , Ling Guixia , Xiang Rongwu , Jiang Xiwei
Published: December 2022

Fibrosis of the liver is a degenerative alteration that occurs in the majority of chronic liver disorders. Further progression can lead to cirrhosis, liver failure, and hepatocellular carcinoma, which can seriously affect the health and lives of patients. The field of liver fibrosis research has flourished in the last 20 years, with approximately 9000 articles retrieved from the Web of Science Core Collection database alone. In order to identify future research hotspots and potential paths in a thorough and scientifically reliable manner, it is important to organize and visualize the research on this topic from a holistic and very general perspective. This study used bibliometric analysis with CiteSpace and VOSviewer software to provide a quantitative analysis, hotspot mining, and commentary of articles published in the field of liver fibrosis over the last 20 years. This bibliometric analysis contains a total of 8994 articles with 45667 authors from 6872 institutions in 97 countries, published in 1371 journals and citing 156 309 references. The literature volume has steadily increased over the last 20 years. Research has focused on gastroenterology and hepatology, pharmacology and pharmacy, and medicine, research, and experimental areas. We found that the pathological mechanisms, diagnostic and quantitative methods, etiology, and antifibrotic strategies constitute the knowledge structure of liver fibrosis. Finding mechanisms for liver fibrosis regression, identifying precise noninvasive diagnostic and prognostic biomarkers, and creating efficient liver fibrosis patient treatments are the main goals of current research.
The Undisciplined Youth and a Moral Panic in Independent India, Circa 1947‐1964
Authors: Wilkinson Tom
Published: December 2022

The undisciplined youth is one figure that is key to understanding the 1950s and 1960s in India. Politicians, officials, academics, youth leaders, and journalists developed and spread a discourse that imagined the collective behaviour of Indian youths as falling well below adult expectations of them in independent India. The imagery of the youth lacking in discipline was tied up with cycles of student unrest and the idea that the methods of protest used during the pre‐independence period had wrongly continued into the post‐independence period, but this discursive formation was often extended to include all Indian youths and it became translated into a long‐term anxiety about the future of the newly established nation‐state. These tropes about the undisciplined Indian youth became a symbol of the country's unresolved future. Unless the crisis of youth could be remedied, the narrative went, then the potentiality of Indian independence and its first generation of citizens could never be realised. This discourse took on a novel and distinctive shape during the initial years following Indian independence in 1947, it crystallised during the early 1950s, and there was a continued build‐up of public concern that lasted throughout the 1960s.
Melatonin ameliorates myocardial infarction in obese diabetic individuals: The possible involvement of macrophage apoptotic factors
Authors: Maity Juin , Dey Tiyasa , Banerjee Adrita , Chattopadhyay Aindrila , Das Asish R. , Bandyopadhyay Debasish
Published: December 2022

In recent days, the hike in obesity‐mediated epidemics across the globe and the prevalence of obesity‐induced cardiovascular disease has become one of the chief grounds for morbidity and mortality. This epidemic‐driven detrimental events in the cardiac tissues start with the altered distribution and metabolism pattern of high‐density lipoprotein and low‐density lipoprotein (LDL) leading to cholesterol (oxidized LDL) deposition on the arterial wall and atherosclerotic plaque generation, followed by vascular spasms and infarction. Subsequently, obesity‐triggered metabolic malfunctions induce free radical generation which may further trigger pro‐inflammatory signaling and nuclear factor kappa‐light‐chain‐enhancer of activated B cells transcriptional factor, thus inducing interferon‐gamma, tumor necrosis factor‐alpha, and inducible nitric oxide synthase. This terrifying cardiomyopathy can be further aggravated in type 2 diabetes mellitus, thereby making obese diabetic patients prone toward the development of myocardial infarction (MI) or stroke in comparison to their nondiabetic counterparts. The accelerated oxidative stress and pro‐inflammatory response induced cardiomyocyte hypertrophy, followed by apoptosis in obese diabetic individuals, causing progression of athero‐thrombotic vascular disease. Being an efficient antioxidative and anti‐inflammatory indolamine, melatonin effectively inhibits lipid peroxidation, pro‐inflammatory reactions, thereby resolving free radical‐induced myocardial damages along with maintaining antioxidant reservoir to preserve cardiovascular integrity. Prolonged melatonin treatment maintains balanced body weight and serum total cholesterol concentration by inhibiting cholesterol synthesis and promoting cholesterol catabolism. Additionally, melatonin promotes macrophage polarization toward the anti‐inflammatory state, providing a proper shield during the recovery period. Therefore, the protective role of melatonin in maintaining the lipid metabolism homeostasis and blocking the atherosclerotic plaque rupture could be targeted as the possible therapeutic strategy for the management of obesity‐induced acute MI. This review aimed at orchestrating the efficacy of melatonin in ameliorating irrevocable oxidative cardiovascular damage induced by the obesity–diabetes correlation.
Abundant copathologies of polyglucosan bodies, frontotemporal lobar degeneration with TDP‐43 inclusions and ageing‐related tau astrogliopathy in a family with aGBE1mutation
Authors: Uemura Maiko T. , Suh Eun Ran , Robinson John L. , Brunden Kurt R. , Grossman Murray , Irwin David J. , Lee Virginia M.‐Y. , Trojanowski John Q. , Lee Edward B. , Van Deerlin Vivianna M.
Published: December 2022

Aims

Adult polyglucosan body disease (APBD) is a progressive neurogenetic disorder caused by 1,4‐alpha‐glucan branching enzyme 1 (GBE1) mutation with an accumulation of polyglucosan bodies (PBs) in the central and peripheral nervous systems as a pathological hallmark. Here, we report two siblings in a family with aGBE1mutation with prominent frontotemporal lobar degeneration with TAR DNA‐binding protein 43 (FTLD‐TDP) and ageing‐related tau astrogliopathy (ARTAG) copathologies with PBs in the central nervous system.

Methods

Whole‐genome sequencing (WGS) followed by Sanger sequencing (SS) was performed on three affected and two unaffected siblings in a pedigree diagnosed with familial frontotemporal dementia. Out of the affected siblings, autopsies were conducted on two cases, and brain samples were used for biochemical and histological analyses. Brain sections were stained with haematoxylin and eosin and immunostained with antibodies against ubiquitin, tau, amyloid β, α‐synuclein, TDP‐43 and fused in sarcoma (FUS).

Results

A novel single nucleotide deletion inGBE1, c.1280delG, was identified, which is predicted to result in a reading frameshift, p.Gly427Glufs*9. This variant segregated with disease in the family, is absent from population databases and is predicted to cause loss of function, a known genetic mechanism for APBD. The affected siblings showed a greater than 50% decrease in GBE protein levels. Immunohistochemical analysis revealed widespread FTLD‐TDP (type A) and ARTAG pathologies as well as PBs in the brains of two affected siblings for whom an autopsy was performed.

Conclusions

This is the first report of a family with several individuals with a FTD clinical phenotype and underlying copathologies of APBD, FTLD‐TDP and ARTAG with a segregatingGBE1loss‐of‐function mutation in affected siblings. The finding of copathologies of APBD and FTLD‐TDP suggests these processes may share a disease mechanism resulting from thisGBE1mutation.
Global dissection of the recombination landscape in soybean using a high‐density 600K SoySNP array
Authors: Ma Xin , Fan Lei , Zhang Zhifang , Yang Xia , Liu Yucheng , Ma Yanming , Pan Yi , Zhou Guoan , Zhang Min , Ning Hailong , Kong Fanjiang , Ma Junkui , Liu Shulin , Tian Zhixi
Published: December 2022

Recombination is crucial for crop breeding because it can break linkage drag and generate novel allele combinations. However, the high‐resolution recombination landscape and its driving forces in soybean are largely unknown. Here, we constructed eight recombinant inbred line (RIL) populations and genotyped individual lines using the high‐density 600K SoySNP array, which yielded a high‐resolution recombination map with 5636 recombination sites at a resolution of 1.37 kb. The recombination rate was negatively correlated with transposable element density and GC content but positively correlated with gene density. Interestingly, we found that meiotic recombination was enriched at the promoters of active genes. Further investigations revealed that chromatin accessibility and active epigenetic modifications promoted recombination. Our findings provide important insights into the control of homologous recombination and thus will increase our ability to accelerate soybean breeding by manipulating meiotic recombination rate.
Red‐light receptor phytochrome B inhibits BZR1‐NAC028‐CAD8B signaling to negatively regulate rice resistance to sheath blight
Authors: Yuan De Peng , Yang Shuo , Feng Lu , Chu Jin , Dong Hai , Sun Jian , Chen Huan , Li Zhuo , Yamamoto Naoki , Zheng Aiping , Li Shuang , Yoon Hong Chan , Chen Jingsheng , Ma Dianrong , Xuan Yuan Hu
Published: December 2022

Phytochrome (Phy)‐regulated light signalling plays important roles in plant growth, development, and stress responses. However, its function in rice defence against sheath blight disease (ShB) remains unclear. Here, we found that PhyB mutation or shade treatment promoted rice resistance to ShB, while resistance was reduced by PhyB overexpression. Further analysis showed that PhyB interacts with phytochrome‐interacting factor‐like 15 (PIL15), brassinazole resistant 1 (BZR1), and vascular plant one‐zinc‐finger 2 (VOZ2). Plants overexpressing PIL15 were more susceptible to ShB in contrast to bzr1‐D‐overexpressing plants compared with the wild‐type, suggesting that PhyB may inhibit BZR1 to negatively regulate rice resistance to ShB. Although BZR1 is known to regulate brassinosteroid (BR) signalling, the observation that BR signalling negatively regulated resistance to ShB indicated an independent role for BZR1 in controlling rice resistance. It was also found that the BZR1 ligand NAC028 positively regulated resistance to ShB. RNA sequencing showed that cinnamyl alcohol dehydrogenase 8B (CAD8B), involved in lignin biosynthesis was upregulated in both bzr1‐D‐ and NAC028‐overexpressing plants compared with the wild‐type. Yeast‐one hybrid, ChIP, and transactivation assays demonstrated that BZR1 and NAC028 activate CAD8B directly. Taken together, the analyses demonstrated that PhyB‐mediated light signalling inhibits the BZR1‐NAC028‐CAD8B pathway to regulate rice resistance to ShB.
Genome‐wide identification and expression analysis of SlRR genes in response to abiotic stress in tomato
Authors: Liu H. , Chen R. , Li H. , Lin J. , Wang Y. , Han M. , Wang T. , Wang H. , Chen Q. , Chen F. , Chu P. , Liang C. , Ren C. , Zhang Y. , Yang F. , Sheng Y. , Wei J. , Wu X. , Yu G.
Published: December 2022

The cytokinin two‐component signal transduction system (TCS) is involved in many biological processes, including hormone signal transduction and plant growth regulation. Although cytokinin TCS has been well characterized in Arabidopsis thaliana, its role in tomato remains elusive.

In this study, we characterized the diversity and function of response regulator (RR) genes, a critical component of TCS, in tomato. In total, we identified 31 RR genes in the tomato genome. These SlRR genes were classified into three subgroups (type‐A, type‐B and type‐C).

Various stress‐responsive cis‐elements were present in the tomato RR gene promoters. Their expression responses under pesticide treatment were evaluated by transcriptome analysis. Their expression under heat, cold, ABA, salinity and NaHCO3 treatments was further investigated by qRT‐PCR and complemented with the available transcription data under these treatments. Specifically, SlRR13 expression was significantly upregulated under salinity, drought, cold and pesticide stress and was downregulated under ABA treatment. SlRR23 expression was induced under salt treatment, while the transcription level of SlRR1 was increased under cold and decreased under salt stress.

We also found that GATA transcription factors played a significant role in the regulation of SlRR genes. Based on our results, tomato SlRR genes are involved in responses to abiotic stress in tomato and could be implemented in molecular breeding approaches to increase resistance of tomato to environmental stresses.
Implications of product substitutability in a distribution channel
Authors: Zheng Quan , Hu Honggang , Pan Xiajun Amy
Published: December 2022

This paper examines the effect of product substitutability on the equilibrium profits in a distribution channel of two symmetric manufacturers selling substitutable products to consumers through a nonexclusive retailer. Conventional wisdom suggests that when the products are more substitutable, the retailer will be better off while the manufacturers will be worse off, owing to the dominance of the competition effect of substitutability. In this work, we identify the hitherto neglected demand effect of substitutability and show that the relative strength between the competition and demand effects is the key to this result. As the products become more substitutable, the upstream competition does intensify, but vitally, the demand may expand. We show that the interests of the retailer and manufacturers can be aligned in terms of product substitutability, depending on both the demand and supply factors. Surprisingly, the conventional result can even be completely reversed such that the manufacturers benefit from a certain level of substitutability for some demand patterns. Assuming linear demand, we further isolate the important role of the bargaining power balance and the alternative of agency selling format in moderating the competition effect. For example, as the retailer gains more bargaining power, the (negative) demand effect can overshadow the (positive) competition effect such that a higher degree of substitutability can actually hurt the retailer. Our findings provide valuable implications for persuasive advertising and category management.
Environmental governance in China: The effects of policy clarity, career concerns, and new appointed officials on pollution control
Authors: Sun Jingran , Yue Linfeng , Li Xiangyu (Dale) , Dai Min
Published: December 2022

In the last three decades, China has taken actions to tackle its environmental issues while the tension between policymakers at the central level and decentralized implementation of such policies has been a major concern. This study investigates how policy clarity and high powered incentive system jointly affect organizational performance in the context of environmental governance in China. Utilizing city‐level data compiled with text data extracted from Report on the Work of the Government from 2004 to 2015 and Difference in Differences (DID) design, we find that the compliance of local officials to protect the environment as well as the actual environmental protection outcome significantly increased. Our study also finds evidence that newly‐appointed Party Secretaries at the city level are the main facilitators of enhancing environmental regulation policies. This research proposes a two by two typology based on the principal‐agent theory explaining how successful environmental governance within this period in China is realized and offers practical implications for those who seek to enhance the effectiveness of environmental governance.
Considerations for challenges with STEM standards alignment in the middle grades
Authors: Gonzales Jennifer A. , Ritter Kenley B. , Shelton Ryann N.
Published: December 2022

Research favors active learning through STEM disciplines to improve understanding; however, opportunities for well‐aligned STEM integration presented challenges for Northside Independent School District (NISD). First, state standards did not align across contents and grade levels. Second, the standardized tests created a lack of flexibility to adjust the pacing and sequencing of instruction. Third, there was a lack of resources that supported each of the content areas in an integrated and aligned STEM learning experience that benefited the individual content areas. To address these needs, Northside ISD used innovative practices to overcome their challenges with writing a middle school STEM curriculum. Despite the lack of resources available, the middle school curriculum and instruction team addressed these challenges by re‐sequencing standards, developing Design Challenge research opportunities, and identifying a unique STEM Context that could be carried throughout an instructional unit. This innovation addressed each core content area with fidelity and allowed for STEM alignment while also exposing students in the district to unique STEM opportunities.
Pepper stress‐associated protein 14 is a substrate of CaSnRK2.6 that positively modulates abscisic acid‐dependent osmotic stress responses
Authors: Bae Yeongil , Lim Chae Woo , Lee Sung Chul
Published: December 2022

The phytohormone abscisic acid (ABA) plays a prominent role in various abiotic stress responses of plants. In the ABA‐dependent osmotic stress response, SnRK2.6, one of the subclass III SnRK2 kinases, has been identified as playing a key role by phosphorylating and activating downstream genes. Although several modulatory proteins have been reported to be phosphorylated by SnRK2.6, the identities of the full spectrum of downstream targets have yet to be sufficiently established. In this study, we identified CaSAP14, a stress‐associated protein in pepper (Capsicum annuum), as a downstream target of CaSnRK2.6. We elucidated the physical interaction between SnRK2.6 and CaSAP14, both in vitro and in vivo, and accordingly identified a C‐terminal C2H2‐type zinc finger domain of CaSAP14 as being important for their interaction. CaSAP14‐silenced pepper plants showed dehydration‐ and high salt‐sensitive phenotypes, whereas overexpression of CaSAP14 in Arabidopsis conferred tolerance to dehydration, high salinity, and mannitol treatment, with plants showing ABA‐hypersensitive phenotypes. Furthermore, an in‐gel kinase assay revealed that CaSnRK2.6 phosphorylates CaSAP14 in response to exogenous ABA, dehydration, and high‐salinity stress. Collectively, these findings suggest that CaSAP14 is a direct substrate of CaSnRK2.6 and positively modulates dehydration‐ and high salinity‐induced osmotic stress responses.
Clinical techniques in veterinary dermatology: Dermoscopy
Authors: Burroughs Dylan L. , Diaz Sandra F.
Published: December 2022

Dermoscopy is a noninvasive, painless, easy‐to‐perform technique used in human and veterinary medicine for rapid and magnified in vivo observation of dermatological lesions and disease. Dermoscopy can lead to a swifter diagnosis and may eliminate the need to perform more invasive diagnostic testing such as skin biopsies. To perform dermoscopy, the clinician needs a dermoscope and a software program equipped with image capture for pattern identification. Two techniques exist for dermoscopy: standard contact, where the dermoscope is applied directly to the patient's skin with the use of a liquid interface, or noncontact, where there is no direct contact between the skin and the dermoscope. The most important criteria to be considered when using dermoscopy are the morphology/arrangement of vascular structures, scaling patterns, colours, follicular abnormalities and specific disease features. Application of dermoscopic findings should always be correlated with the patient's history, clinical signs and the morphology of the skin lesions. Dermoscopy does require an initial financial and time investment by the clinician, yet this technique can quickly and easily help to identify patterns of disease that correlate with clinical diagnosis of dermatological disease.
Assessment of survey radiography as a method of diagnosing bilateral laryngeal paralysis in dogs
Authors: Touzet Chloe , Hahn Harriet , Gomes Eymeric , Bismuth Camille , Le Boedec Kevin
Published: December 2022

The gold standard for diagnosis of laryngeal paralysis is laryngoscopy under light anesthesia. This prospective analytical cross‐sectional study aimed to determine whether a radiographic assessment of the larynx could be used as a non‐invasive screening tool for diagnosing laryngeal paralysis in non‐sedated animals, as the laryngeal ventricles may appear wider in affected animals. The laryngeal ventricles of 18 dogs with bilateral laryngeal paralysis composing the affected group and 25 non‐sedated dogs presenting no respiratory abnormality composing the control group were evaluated using right lateral radiography of the larynx. Three observers measured the ratios of the maximal ventricular length and surface to the body length of the third cervical vertebra (MVL/LC3 and VS/LC3, respectively). They also subjectively assessed the ventricular shape as either normal or rounded. The most accurate criterion was found to be MVL/LC3, as the respective areas under the ROC curves were 0.96 (95% confidence interval [CI]: 0.95–0.97), 0.89 (95% CI: 0.87–0.91), 0.80 (95% CI: 0.65–0.95) for MVL/LC3, VS/LC3, and ventricular shape evaluation, respectively. Based on ROC curve analysis, two thresholds of clinical interest were set for the MVL/LC3; bilateral laryngeal paralysis was very unlikely for values < 0.3 and very likely for values > 0.5. The findings of this study support the use of lateral laryngeal radiography as a screening tool for diagnosing bilateral laryngeal paralysis. However, further diagnostic tests remain required if MVL/LC3 lies between these threshold values or if clinically indicated. Further studies are warranted to explore the use of laryngeal radiography in unilateral paralysis and other laryngeal or oropharyngeal diseases.
Management and outcomes of 13 dogs treated with a modified Heller myotomy and Dor fundoplication for lower esophageal sphincter achalasia‐like syndrome
Authors: Winston John M. , Mann F. A. (Tony) , Dean Lauren
Published: December 2022

Objective

To report the management and outcomes of dogs treated for lower esophageal sphincter achalasia‐like syndrome (LES‐AS) with modified Heller myotomy, Dor fundoplication, and with the use of a temporary gastrostomy tube.

Study design

Retrospective.

Sample population

Thirteen client‐owned dogs.

Methods

Medical records and a client survey were used to assess frequency of vomiting/regurgitation, quality of life (QoL), bodyweight, and feeding modifications at the following time points: prior to referral, postoperatively from discharge to first recheck (4‐6 weeks), and from first recheck to survey (48 months). Postoperative and gastrostomy tube complications were surveyed and recorded. Pretreatment and 4‐6 weeks postoperative videofluoroscopic swallow studies (VFSS) were compared. Two‐sided t‐tests were used to compare outcomes between survey time points.

Results

Postoperative VFSS scores (available in 9 dogs) improved over preoperative scores in 6 dogs, and 12/13 dogs survived to discharge. One dog was euthanized 3 days postoperatively due to aspiration pneumonia. Postoperative gastrostomy tube complications occurred in half of the dogs that survived to discharge. According to the owners, scores assigned to vomiting/regurgitation improved by 180% (P = .004), QoL by 100% (P = .004), and bodyweight by 63% (P = .035).

Conclusion

Modified Heller myotomy with Dor fundoplication and the use of a temporary gastrostomy tube improved clinical signs and owners' perceived quality of life in half of the dogs treated for LES‐AS in our clinical setting. Oral sildenafil therapy discontinued postoperatively suggests that surgery was equally efficacious.

Clinical significance

Modified Heller myotomy with Dor fundoplication and temporary gastrostomy tube is a treatment option with potentially sustained benefits for dogs that have LES‐AS.
Quadratic characters with positive partial sums
Authors: Kalmynin A. B.
Published: December 2022

Let be the set of all primes p for which the sums of over the interval [1, N] are non‐negative for all N. We prove that the estimate
holds for .
Experiences of patients and their family members with metachromatic leukodystrophy, adrenoleukodystrophy, and Krabbe disease: a qualitative systematic review protocol
Authors: Koto Yuta , Ueki Shingo , Yamakawa Miyae , Sakai Norio
Published: December 2022

Objective:

The objective of this review is to synthesize the experiences of patients with metachromatic leukodystrophy (MLD), adrenoleukodystrophy (ALD), and Krabbe disease and the experiences of their family members.

Introduction:

MLD, ALD, and Krabbe disease are rare disorders that are classified as lysosomal storage or peroxisomal disorders, with similar presentations as leukodystrophy. As these diseases cause cognitive and neurological decline due to the progression of leukodystrophy associated with demyelination, they have significant impact on the lives of patients and their families. It is important to identify the impact and challenges of these diseases on patients’ lives and on their families, as well as to synthesize qualitative studies regarding their experiences.

Inclusion criteria:

We will consider studies including patients with MLD, ALD, or Krabbe disease and their family members. These experiences will include the challenges, dissatisfactions, and frustrations with symptoms and treatments; complications of hematopoietic stem cell transplantation; and the increased caregiver burden with disease progression. This is important since the impacts of disease progression are experienced in a variety of settings beyond the hospital, such as in the community and at home.

Methods:

The search strategy will follow JBI methodology and be conducted in 3 steps: an initial limited search, a comprehensive database search, and a reference search of the included articles. MEDLINE, CINAHL Plus, PsycINFO, and Scopus will be searched with no restriction on language or publication dates. The study selection, critical appraisal, data extraction, and data synthesis will be performed according to JBI guidelines for systematic reviews of qualitative research. Final syntheses will be assessed using the ConQual approach.

Systematic review registration number:

PROSPERO CRD42022318805.
From Scan to Simulation—A Novel Workflow for Developing Bioinspired Heart Valves
Authors: Lee Aeryne , Farajikhah Syamak , Crago Matthew , Mosse Luke , Fletcher David Frederick , Dehghani Fariba , Winlaw David Scott , Naficy Sina
Published: December 2022

Current heart valve replacements lack durability and prolonged performance, especially in pediatric patients. In part, these problems may be attributed to the materials chosen for these constructs, but another important contributing factor is the design of the valve, as this dictates hemodynamic performance and impacts leaflet stresses which may accelerate structural valve deterioration. Most current era bioprosthetic valves adhere to a fundamental design where flat leaflets are supported by commissural posts, secured to a sewing ring. This overall design strategy is effective, but functionality and durability can be improved by incorporating features of the native valve geometry. This paper presents a novel workflow for developing and analyzing bio-inspired valve designs computationally. The leaflet curvature was defined using a mathematical equation whose parameters were derived from the three-dimensional model of a native sheep pulmonary valve obtained via microcomputed tomography. Finite element analysis was used to screen the various valve designs proposed in this study by assessing the effect of leaflet thickness, Young's modulus, and height/curvature on snap-through (where leaflets bend against their original curvature), geometric orifice area (GOA) and the stress in the leaflets. This workflow demonstrated benefits for valve designs with leaflet thicknesses between 0.1 and 0.3 mm, Young's moduli less than 50 MPa, and elongated leaflets with higher curvatures. The proposed workflow brings substantial efficiency gains at the design stage, minimizing manufacturing and animal testing during iterative improvements, and offers a bridge between in vitro and more complex in silico studies in the future.
Frequency dependence of sensitivity to interaural phase differences in pure tones
Authors: Klug Jonas , Dietz Mathias
Published: December 2022

It is well established that in normal-hearing humans, the threshold of interaural time differences for pure tones increases dramatically above about 1300 Hz, only to become unmeasurable above 1400 Hz. However, physiological data and auditory models suggest that the actual decline in sensitivity is more gradual and only appears to be abrupt because the maximum of the psychometric function dips below the threshold proportion correct, e.g., 0.794. Published data only report thresholds at certain proportions correct but not the decline of proportions correct or of the sensitivity index d′ with increasing frequencies. Here, we present pure-tone behavioral data obtained with a constant stimulus procedure. Seven of nine subjects showed proportions correct above 0.9 at 1300 Hz and virtually no sensitivity at 1500 Hz (proportion correct within 0.07 of chance level). This corresponds to a sensitivity decline of 46–78 dB/oct, much steeper than predicted by existing models or by the decline of phase locking of the auditory nerve fibers in animal data.
Defining functional spatial boundaries using a spatial release from masking task
Authors: Ozmeral Erol J. , Higgins Nathan C.
Published: December 2022

The classic spatial release from masking (SRM) task measures speech recognition thresholds for discrete separation angles between a target and masker. Alternatively, this study used a modified SRM task that adaptively measured the spatial-separation angle needed between a continuous male target stream (speech with digits) and two female masker streams to achieve a specific SRM. On average, 20 young normal-hearing listeners needed less spatial separation for 6 dB release than 9 dB release, and the presence of background babble reduced across-listener variability on the paradigm. Future work is needed to better understand the psychometric properties of this adaptive procedure.
Acoustic identification and classification of four dolphin species in the Brazilian marine area affected by the largest tailings dam failure disaster
Authors: Amorim Thiago O. S. , Castro Franciele R. de , Ferreira Giovanne A. , Neri Fernanda M. , Duque Bruna R. , Mura João P. , Andriolo Artur
Published: December 2022

Passive acoustic monitoring (PAM) is an increasingly used technique to access the occurrence, distribution, and abundance of cetaceans that may be visually unavailable most of the time. The largest tailings dam failure disaster occurred on 5 November 2015, when the Fundão dam collapsed, releasing over 50 million cubic meters of tailings into the Doce River basin; 14 days later, the tailings plume reached the Atlantic Ocean. PAM was implemented in the concerned area and cetacean species were acoustically identified. Whistles and clicks of visual and acoustic matches were used to predict and classify exclusive acoustic records through random forest models. The identified species were Guiana, rough-toothed, and bottlenose dolphins. Additionally, the franciscana, the most threatened cetacean in the western South Atlantic Ocean, was also acoustically identified. The whistle classifier had 86.9% accuracy with final frequency, duration, and maximum frequency ranked as the most important parameters. The clicks classifier had 86.7% accuracy with peak frequency and 3 dB bandwidth as the most important parameters for classifying species. Considering the potential effect of the increase in turbidity on sound transmission, such as attenuation, the presented classifier should be continuously improved with novel data collected from long-term acoustic monitoring.
Lifetime risk of imprisonment in the United States remains high and starkly unequal
Authors: Roehrkasse Alexander F. , Wildeman Christopher
Published: December 2022

How likely are U.S. males and females of different ethnoracial groups to be imprisoned over the course of their lives, and how have these risks changed in recent decades? Using survey and administrative data, we update 20th-century estimates of the cumulative risk of imprisonment for the 21st century. In 2016, non-Hispanic Black males’ lifetime risk of imprisonment remained very high—more than 16%—but decreased substantially relative to extreme levels of risk in the 1990s and early 2000s. The lifetime risk of imprisonment among people identifying as American Indian or Alaska Native was nearly 50% for males and more than 14% for females. Although national prison admission rates are declining, imprisonment remains a pervasive and highly unequal life-course experience.
Perovskite grain wrapping by converting interfaces and grain boundaries into robust and water-insoluble low-dimensional perovskites
Authors: Jiao Haoyang , Ni Zhenyi , Shi Zhifang , Fei Chengbin , Liu Ye , Dai Xuezeng , Huang Jinsong
Published: December 2022

Stabilizing perovskite solar cells requires consideration of all defective sites in the devices. Substantial efforts have been devoted to interfaces, while stabilization of grain boundaries received less attention. Here, we report on a molecule tributyl(methyl)phosphonium iodide (TPI), which can convert perovskite into a wide bandgap one-dimensional (1D) perovskite that is mechanically robust and water insoluble. Mixing TPI with perovskite precursor results in a wrapping of perovskite grains with both grain surfaces and grain boundaries converted into several nanometer-thick 1D perovskites during the grain formation process as observed by direct mapping. The grain wrapping passivates the grain boundaries, enhances their resistance to moisture, and reduces the iodine released during light soaking. The perovskite films with wrapped grains are more stable under heat and light. The best device with wrapped grains maintained 92.2% of its highest efficiency after light soaking under 1-sun illumination for 1900 hours at 55°C open-circuit condition.
Limpet teeth microstructure unites auxeticity with extreme strength and high stiffness
Authors: Oh Sang Ho , Kim Jin-Kyung , Liu Yue , Wurmshuber Michael , Peng Xiang-Long , Seo Jinsol , Jeong Jiwon , Wang Zhen , Wilmers Jana , Soyarslan Celal , Kim Jongil , Kittiwirayanon Boonsita , Jeong Jeehun , Kim Hyo-Jeong , Huh Yang Hoon , Kiener Daniel , Bargmann Swantje , Gao Huajian
Published: December 2022

Materials displaying negative Poisson’s ratio, referred to as auxeticity, have been found in nature and created in engineering through various structural mechanisms. However, uniting auxeticity with high strength and high stiffness has been challenging. Here, combining in situ nanomechanical testing with microstructure-based modeling, we show that the leading part of limpet teeth successfully achieves this combination of properties through a unique microstructure consisting of an amorphous hydrated silica matrix embedded with bundles of single-crystal iron oxide hydroxide nanorods arranged in a pseudo-cholesteric pattern. During deformation, this microstructure allows local coordinated displacement and rotation of the nanorods, enabling auxetic behavior while maintaining one of the highest strengths among natural materials. These findings lay a foundation for designing biomimetic auxetic materials with extreme strength and high stiffness.
Route of self-amplifying mRNA vaccination modulates the establishment of pulmonary resident memory CD8 and CD4 T cells
Authors: Künzli Marco , O’Flanagan Stephen D. , LaRue Madeleine , Talukder Poulami , Dileepan Thamotharampillai , Stolley J. Michael , Soerens Andrew G. , Quarnstrom Clare F. , Wijeyesinghe Sathi , Ye Yanqi , McPartlan Justine S. , Mitchell Jason S. , Mandl Christian W. , Vile Richard , Jenkins Marc K. , Ahmed Rafi , Vezys Vaiva , Chahal Jasdave S. , Masopust David
Published: December 2022

Respiratory tract resident memory T cells (T
RM
), typically generated by local vaccination or infection, can accelerate control of pulmonary infections that evade neutralizing antibody. It is unknown whether mRNA vaccination establishes respiratory T
RM
. We generated a self-amplifying mRNA vaccine encoding the influenza A virus nucleoprotein that is encapsulated in modified dendron–based nanoparticles. Here, we report how routes of immunization in mice, including contralateral versus ipsilateral intramuscular boosts, or intravenous and intranasal routes, influenced influenza-specific cell–mediated and humoral immunity. Parabiotic surgeries revealed that intramuscular immunization was sufficient to establish CD8 T
RM
in the lung and draining lymph nodes. Contralateral, compared with ipsilateral, intramuscular boosting broadened the distribution of lymph node T
RM
and T follicular helper cells but slightly diminished resulting levels of serum antibody. Intranasal mRNA delivery established modest circulating CD8 and CD4 T cell memory but augmented distribution to the respiratory mucosa. Combining intramuscular immunizations with an intranasal mRNA boost achieved high levels of both circulating T cell memory and lung T
RM
. Thus, routes of mRNA vaccination influence humoral and cell-mediated immunity, and intramuscular prime-boosting establishes lung T
RM
that can be further expanded by an additional intranasal immunization.
Eocene magmatism in the Himalaya: Response to lithospheric flexure during early Indian collision?
Authors: Ma Lin , Wang Qiang , Kerr Andrew C. , Li Zheng-Xiang , Dan Wei , Yang Ya-Nan , Zhou Jin-Sheng , Wang Jun , Li Cheng
Published: December 2022

Eocene mafic magmatism in the Himalaya provides a crucial window for probing the evolution of crustal anatexis processes within the lower plate in a collisional orogen. We report geochemical data from the earliest postcollision ocean-island basalt–like mafic dikes intruding the Tethyan Himalaya near the northern edge of the colliding Indian plate. These dikes occurred coeval, and spatially overlap, with Eocene granitoids in the cores of gneiss domes and were likely derived from interaction between melts from the lithosphere-asthenosphere boundary and the Indian continental lithosphere. We propose that these mafic magmas were emplaced along lithospheric fractures in response to lithospheric flexure during initial subduction of the Indian continent and that the underplating of such mafic magmas resulted in orogen-parallel crustal anatexis within the Indian continent. This mechanism can explain the formation of coeval magmatism and the geologic evolution of a collisional orogen on both sides of the suture zone.
Preferential preservation of low-elevation biotas in the nonmarine fossil record
Authors: Holland Steven M. , Loughney Katharine M. , Cone Marjean
Published: December 2022

Modern coastal sedimentary basins typically lie at low elevations (<600 m), whereas inland basins commonly occupy elevations as high as 4000–5000 m. Individual basins of all types typically preserve a narrower span of elevations, generally <1000 m, and typically near 200–300 m in coastal basins. As a result, the nonmarine fossil record is expected to preserve mainly low-elevation habitats and a relatively narrow range of elevations. Because many of the basins that preserve high elevations are likely to undergo subsequent destruction via erosion or continental collision, the dominance of low-elevation habitats is likely to become stronger into deep time. This selective preservation of nonmarine communities from sedimentary basins, and specifically from low elevations, suggests that much or even most of ancient nonmarine biodiversity is not preserved. Given the occurrence of many modern biodiversity hotspots in regions of high elevation, long ghost lineages are likely common in the nonmarine fossil record, and divergence times estimated from the nonmarine fossil record may be systematically far too short. The spans of elevations that are preserved in sedimentary basins suggest that the fossil record may preserve gradients in community composition that are correlated with elevation, yet they have been largely undetected.
Supplemental Material: Plumbing the depths of magma crystallization using 176Lu/177Hf in zircon as a pressure proxy
Authors: Moreira Hugo , al. et
Published: December 2022

Supplemental information, Figures S1–S5, Tables S1–S9, and Data Sets S1–S4. 
User-centred design for machine learning in health care: a case study from care management
Authors: Seneviratne Martin G , Li Ron C , Schreier Meredith , Lopez-Martinez Daniel , Patel Birju S , Yakubovich Alex , Kemp Jonas B , Loreaux Eric , Gamble Paul , El-Khoury Kristel , Vardoulakis Laura , Wong Doris , Desai Janjri , Chen Jonathan H , Morse Keith E , Downing N Lance , Finger Lutz T , Chen Ming-Jun , Shah Nigam
Published: December 2022

Objectives

Few machine learning (ML) models are successfully deployed in clinical practice. One of the common pitfalls across the field is inappropriate problem formulation: designing ML to fit the data rather than to address a real-world clinical pain point.

Methods

We introduce a practical toolkit for user-centred design consisting of four questions covering: (1) solvable pain points, (2) the unique value of ML (eg, automation and augmentation), (3) the actionability pathway and (4) the model’s reward function. This toolkit was implemented in a series of six participatory design workshops with care managers in an academic medical centre.

Results

Pain points amenable to ML solutions included outpatient risk stratification and risk factor identification. The endpoint definitions, triggering frequency and evaluation metrics of the proposed risk scoring model were directly influenced by care manager workflows and real-world constraints.

Conclusions

Integrating user-centred design early in the ML life cycle is key for configuring models in a clinically actionable way. This toolkit can guide problem selection and influence choices about the technical setup of the ML problem.