bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes in patients with spontaneous bacterial peritonitis utilizing first-line or alternative agents for secondary prophylaxis
Authors: Collette Kaylyn , Bethea Audis , Schadler Aric , Kelley Jordan L
Published: January 2023

Purpose

The American Association for the Study of Liver Diseases guidelines recommend ciprofloxacin as a first-line option for spontaneous bacterial peritonitis (SBP) prophylaxis, citing literature that is over 30 years old. There is insufficient data and guidance for prophylaxis in cases of fluoroquinolone treatment failure or intolerance. This study aimed to evaluate outcomes in patients whose antimicrobial prophylaxis was switched from first-line therapies to an alternative agent versus those who were not switched following recurrent SBP.

Methods

This study was an institutional review board–approved retrospective chart review of patients admitted to University of Kentucky HealthCare from 2014 through 2020. Patients included were 18 years of age or older with a diagnosis of recurrent SBP. The primary outcome examined was SBP recurrence rate following initial prophylaxis failure. Additional analyses targeted secondary outcomes, including 6-month mortality, development of SBP complications, development of an adverse drug reaction, and development of multidrug-resistant pathogens.

Results

Fifty-three patients were identified with recurrent SBP and divided into 2 cohorts: 25 patients were switched from their original prophylactic agent while 28 patients continued on the same agent after SBP recurrence. Patients in the switch group had lower rates of recurrence (52% vs 100%). Additionally, these patients had lower 6-month mortality rates (24% vs 57.1%; P = 0.015). Thirteen patients in the no-switch group and 3 patients in the switch group required intensive care on a subsequent admission (46.4% vs 12%; P = 0.008). There were no significant differences between the groups in rates of other SBP complications.

Conclusion

Patients switched from their original prophylactic agent had lower rates of SBP recurrence with significantly lower 6-month mortality rates.
Historical biogeography and local adaptation explain population genetic structure in a widespread terrestrial orchid
Authors: Evans Alexandra , de Kort Hanne , Brys Rein , Duffy Karl J , Jersáková Jana , Kull Tiiu , Selosse Marc-André , Tsiftsis Spyros , Minasiewicz Julita , Jacquemyn Hans
Published: January 2023

Background and Aims

Historical changes in environmental conditions and colonization–extinction dynamics have a direct impact on the genetic structure of plant populations. However, understanding how past environmental conditions influenced the evolution of species with high gene flow is challenging when signals for genetic isolation and adaptation are swamped by gene flow. We investigated the spatial distribution and genetic structure of the widespread terrestrial orchid Epipactis helleborine to identify glacial refugia, characterize postglacial population dynamics and assess its adaptive potential.

Methods

Ecological niche modelling was used to locate possible glacial refugia and postglacial recolonization opportunities of E. helleborine. A large single-nucleotide polymorphism (SNP) dataset obtained through genotyping by sequencing was used to define population genetic diversity and structure and to identify sources of postglacial gene flow. Outlier analyses were used to elucidate how adaptation to the local environment contributed to population divergence.

Key Results

The distribution of climatically suitable areas was restricted during the Last Glacial Maximum to the Mediterranean, south-western Europe and small areas in the Alps and Carpathians. Within-population genetic diversity was high in E. helleborine (mean expected heterozygosity, 0.373 ± 0.006; observed heterozygosity, 0.571 ± 0.012; allelic richness, 1.387 ± 0.007). Italy and central Europe are likely to have acted as important genetic sources during postglacial recolonization. Adaptive SNPs were associated with temperature, elevation and precipitation.

Conclusions

Forests in the Mediterranean and Carpathians are likely to have acted as glacial refugia for Epipactis helleborine. Postglacial migration northwards and to higher elevations resulted in the dispersal and diversification of E. helleborine in central Europe and Italy, and to geographical isolation and divergent adaptation in Greek and Italian populations. Distinguishing adaptive from neutral genetic diversity allowed us to conclude that E. helleborine has a high adaptive potential to climate change and demonstrates that signals of adaptation and historical isolation can be identified even in species with high gene flow.
Genomic, spatial and morphometric data for discrimination of four species in the Mediterranean Tamus clade of yams (Dioscorea, Dioscoreaceae)
Authors: Campos Miguel , Kelley Emma , Gravendeel Barbara , Médail Frédéric , Maarten Christenhusz J M , Fay Michael F , Catalán Pilar , Leitch Ilia J , Forest Félix , Wilkin Paul , Viruel Juan
Published: January 2023

Background and Aims

Among the numerous pantropical species of the yam genus, Dioscorea, only a small group occurs in the Mediterranean basin, including two narrow Pyrenean endemics (Borderea clade) and two Mediterranean-wide species (D. communis and D. orientalis, Tamus clade). However, several currently unrecognized species and infraspecific taxa have been described in the Tamus clade due to significant morphological variation associated with D. communis. Our overarching aim was to investigate taxon delimitation in the Tamus clade using an integrative approach combining phylogenomic, spatial and morphological data.

Methods

We analysed 76 herbarium samples using Hyb-Seq genomic capture to sequence 260 low-copy nuclear genes and plastomes, together with morphometric and environmental modelling approaches.

Key Results

Phylogenomic reconstructions confirmed that the two previously accepted species of the Tamus clade, D. communis and D. orientalis, are monophyletic and form sister clades. Three subclades showing distinctive geographic patterns were identified within D. communis. These subclades were also identifiable from morphometric and climatic data, and introgression patterns were inferred between subclades in the eastern part of the distribution of D. communis.

Conclusions

We propose a taxonomy that maintains D. orientalis, endemic to the eastern Mediterranean region, and splits D. communis sensu lato into three species: D. edulis, endemic to Macaronesia (Canary Islands and Madeira); D. cretica, endemic to the eastern Mediterranean region; and D. communis sensu stricto, widespread across western and central Europe. Introgression inferred between D. communis s.s. and D. cretica is likely to be explained by their relatively recent speciation at the end of the Miocene, disjunct isolation in eastern and western Mediterranean glacial refugia and a subsequent westward recolonization of D. communis s.s. Our study shows that the use of integrated genomic, spatial and morphological approaches allows a more robust definition of species boundaries and the identification of species that previous systematic studies failed to uncover.
Transfer of quercetin ingested by maternal mice to neonatal mice via breast milk
Authors: Fujiwara Nao , Mukai Rie , Nishikawa Miyu , Ikushiro Shinichi , Murakami Akira , Ishisaka Akari
Published: January 2023

This is the first study that quantified quercetin (QUE) and its 16 metabolites in the breast milk of QUE-fed maternal mice, the plasma and urine of that, and neonatal mice. Interestingly, the QUE aglycone concentration in the milk was much higher than in the plasma of maternal mice, suggesting that QUE may exert biological activity in neonates.
Keratinocytes and immune cells in the epidermis are key drivers of inflammation in hidradenitis suppurativa providing a rationale for novel topical therapies
Authors: Schell Stephanie L , Cong Zhaoyuan , Sennett Mackenzie L , Gettle Samantha L , Longenecker Amy L , Goldberg Stephanie R , Kirby Joslyn S , Helm Matthew F , Nelson Amanda M
Published: January 2023

Background

Hidradenitis suppurativa (HS) is a debilitating inflammatory skin disease characterized by painful nodules, drainage and scarring in skin folds. Injectable adalimumab is the only drug approved by the US Food and Drug Administration for the treatment of HS. Although systemic Janus kinase (JAK) inhibitors show promise, serious side-effects have been reported. There are no highly effective topical treatments for HS; furthermore, the contribution of epidermal keratinocytes to the intense inflammation has largely been unexplored.

Objectives

We investigated the role of keratinocytes and epidermal immune cells in HS inflammation at all Hurley stages of disease severity. We aimed to determine whether ruxolitinib can mitigate inflammation from keratinocytes and to develop a better understanding of how topical therapeutics might benefit patients with HS.

Methods

We used skin samples from 87 patients with HS (Hurley stages I–III) and 39 healthy controls to compare keratinocyte- and immune cell-driven epidermal inflammation, in addition to the response of lesional HS keratinocytes to treatment with interferon (IFN)-γ and ruxolitinib. We used haematoxylin and eosin staining, immunohistochemistry, immunoblotting and quantitative reverse-transcription polymerase chain reaction assessments in whole skin, isolated epidermis, and cultured keratinocytes from healthy controls and both nonlesional and lesional HS skin to identify and define epidermal and keratinocyte-mediated inflammation in HS and how this may be targeted by therapeutics.

Results

HS lesional keratinocytes autonomously secreted high levels of chemokines, such as CCL2, CCL3 and CXCL3, which recruited neutrophils, CD8 T cells, and natural killer cells to the epidermis. Keratinocytes were the dominant source of tumour necrosis factor-α and interleukin (IL)-6 in HS lesions with little to no contribution from underlying dermal immune cells. In the presence of IFN-γ, which is dependent on immune cell infiltrate in vivo, keratinocytes expressed increased levels of additional cytokines including IL-1β, IL-12, IL-23 and IL-36γ. The JAK inhibitor ruxolitinib mitigated the expression of inflammatory cytokines and chemokines in HS lesional keratinocytes, thus providing a rationale for future study as a topical treatment for HS.

Conclusions

This study demonstrates that keratinocytes actively recruit immune cells to HS epidermis and interactions between these cells drive a broad inflammatory profile in HS epidermis. Targeting epidermal inflammation in HS with novel topical formulations may be highly efficacious with reduced systemic side-effects.
Skin 11β-hydroxysteroid dehydrogenase type 1 enzyme expression regulates burn wound healing and can be targeted to modify scar characteristics
Authors: Tsai Kevin H-Y , Shi Huaikai , Parungao Roxanne J , Naficy Sina , Ding Xiaotong , Ding Xiaofeng , Hew Jonathan J , Wang Xiaosuo , Chrzanowski Wojciech , Lavery Gareth G , Li Zhe , Issler-Fisher Andrea C , Chen Jun , Tan Qian , Maitz Peter K , Cooper Mark S , Wang Yiwei
Published: January 2023

Background

Excessive scarring and fibrosis are the most severe and common complications of burn injury. Prolonged exposure to high levels of glucocorticoids detrimentally impacts on skin, leading to skin thinning and impaired wound healing. Skin can generate active glucocorticoids locally through expression and activity of the 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1). We hypothesised that burn injury would induce 11β-HSD1 expression and local glucocorticoid metabolism, which would have important impacts on wound healing, fibrosis and scarring. We additionally proposed that pharmacological manipulation of this system could improve aspects of post-burn scarring.

Methods

Skin 11β-HSD1 expression in burns patients and mice was examined. The impacts of 11β-HSD1 mediating glucocorticoid metabolism on burn wound healing, scar formation and scar elasticity and quality were additionally examined using a murine 11β-HSD1 genetic knockout model. Slow-release scaffolds containing therapeutic agents, including active and inactive glucocorticoids, were developed and pre-clinically tested in mice with burn injury.

Results

We demonstrate that 11β-HSD1 expression levels increased substantially in both human and mouse skin after burn injury. 11β-HSD1 knockout mice experienced faster wound healing than wild type mice but the healed wounds manifested significantly more collagen deposition, tensile strength and stiffness, features characteristic of excessive scarring. Application of slow-release prednisone, an inactive glucocorticoid, slowed the initial rate of wound closure but significantly reduced post-burn scarring via reductions in inflammation, myofibroblast generation, collagen production and scar stiffness.

Conclusions

Skin 11β-HSD1 expression is a key regulator of wound healing and scarring after burn injury. Application of an inactive glucocorticoid capable of activation by local 11β-HSD1 in skin slows the initial rate of wound closure but significantlyimproves scar characteristics post burn injury.
The Containment Bias of the WHO International Health Regulations
Authors: Le Moli Ginevra
Published: January 2023

The ordinary meaning of the term ‘prevention’ is to prevent harm from occurring. But what ‘harm’? For over 170 years, the system now embodied in the World Health Organization’s (WHO) International Health Regulations (IHRs) has answered this question by focusing on the prevention of disease ‘spread’ across countries, rather than on the ‘spillover’ of pathogens from animals to humans, which constitute the main source of pandemic risk today. This bias towards the containment of disease has deep roots. In the historical context from the IHRs emerged, focusing on pathogen spillover was beyond the possibilities of the science of the time; it was also pointless to the extent that the effort focused on pathogens which were already prevalent in humans, causing diseases such as cholera or plague. Transposed to the present day, this containment bias has important consequences for global health governance. Most importantly among these is that the global health security architecture still lacks a specific system to prevent spillovers of pathogens at the origin of outbreaks and subsequent spread of diseases such as COVID-19, SARS, MERS or Ebola. This article investigates the roots of this focus on containment. Relying on the proceedings of the International Sanitary Conferences that preceded the IHRs, as well as on an untapped documentary archive relating to the revision of the IHRs between 1995-2005, the article explains the reasons underpinning this enduring bias and its implications for global health governance.
Prevalence and Clinical Outcomes of Respiratory Syncytial Virus vs Influenza in Adults Hospitalized With Acute Respiratory Illness From a Prospective Multicenter Study
Authors: Begley Katherine M , Monto Arnold S , Lamerato Lois E , Malani Anurag N , Lauring Adam S , Talbot H Keipp , Gaglani Manjusha , McNeal Tresa , Silveira Fernanda P , Zimmerman Richard K , Middleton Donald B , Ghamande Shekhar , Murthy Kempapura , Kim Lindsay , Ferdinands Jill M , Patel Manish M , Martin Emily T
Published: January 2023

Background

Current understanding of severe respiratory syncytial virus (RSV) infections in adults is limited by clinical underrecognition. We compared the prevalence, clinical characteristics, and outcomes of RSV infections vs influenza in adults hospitalized with acute respiratory illnesses (ARIs) in a prospective national surveillance network.

Methods

Hospitalized adults who met a standardized ARI case definition were prospectively enrolled across 3 respiratory seasons from hospitals participating across all sites of the US Hospitalized Adult Influenza Vaccine Effectiveness Network (2016–2019). All participants were tested for RSV and influenza using real-time reverse-transcription polymerase chain reaction assay. Multivariable logistic regression was used to test associations between laboratory-confirmed infection and characteristics and clinical outcomes.

Results

Among 10 311 hospitalized adults, 6% tested positive for RSV (n = 622), 18.8% for influenza (n = 1940), and 75.1% negative for RSV and influenza (n = 7749). Congestive heart failure (CHF) or chronic obstructive pulmonary disease (COPD) was more frequent with RSV than influenza (CHF: 37.3% vs 28.8%, P < .0001; COPD: 47.6% vs 35.8%, P < .0001). Patients with RSV more frequently had longer admissions (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.06–1.80) for stays >1 week) and mechanical ventilation (OR, 1.45; 95% CI, 1.09–1.93) compared with influenza but not compared with the influenza-negative group (OR, 1.03; 95% CI, .82–1.28 and OR, 1.17; 95% CI, .91–1.49, respectively).

Conclusions

The prevalence of RSV across 3 seasons was considerable. Our findings suggest that those with RSV have worse outcomes compared with influenza and frequently have cardiopulmonary conditions. This study informs future vaccination strategies and underscores a need for RSV surveillance among adults with severe ARI.
Leukocyte Count and Coronary Artery Disease Events in People With Human Immunodeficiency Virus: A Longitudinal Study
Authors: Avery Emma F , Kleynhans Julia N , Ledergerber Bruno , Schoepf Isabella C , Thorball Christian W , Kootstra Neeltje A , Reiss Peter , Ryom Lene , Braun Dominique L , Thurnheer Maria C , Marzolini Catia , Seneghini Marco , Bernasconi Enos , Cavassini Matthias , Buvelot Hélène , Kouyos Roger D , Fellay Jacques , Günthard Huldrych F , Tarr Philip E ,   for the Swiss HIV Cohort Study, Anagnostopoulos A , Battegay M , Bernasconi E , Boni J , Braun DL , Bucher HC , Calmy A , Cavassini M , Ciuffi A , Dollenmaier G , Egger M , Elzi L , Fehr J , Fellay J , Furrer H , Fux CA , Gunthard HF , Haerry D , Hasse B , Hirsch HH , Hoffmann M , Hosli I , Huber M , Kahlert CR , Kaiser L , Keiser O , Klimkait T , Kouyos RD , Kovari H , Ledergerber B , Martinetti G , de Martinez Tejada B , Marzolini C , Metzner KJ , Muller N , Nicca D , Paioni P , Pantaleo G , Perreau M , Rauch A , Rudin C , Scherrer AU , Schmid P , Speck R , Stockle M , Tarr P , Trkola A , Vernazza P , Wandeler G , Weber R , Yerly S
Published: January 2023

Background

People with human immunodeficiency virus (HIV; PWH) have increased cardiovascular risk. Higher leukocyte count has been associated with coronary artery disease (CAD) events in the general population. It is unknown whether the leukocyte-CAD association also applies to PWH.

Methods

In a case-control study nested within the Swiss HIV Cohort Study, we obtained uni- and multivariable odds ratios (OR) for CAD events, based on traditional and HIV-related CAD risk factors, leukocyte count, and confounders previously associated with leukocyte count.

Results

We included 536 cases with a first CAD event (2000–2021; median age, 56 years; 87% male; 84% with suppressed HIV RNA) and 1464 event-free controls. Cases had higher latest leukocyte count before CAD event than controls (median [interquartile range], 6495 [5300–7995] vs 5900 [4910–7200]; P < .01), but leukocytosis (>11 000/µL) was uncommon (4.3% vs 2.1%; P = .01). In the highest versus lowest leukocyte quintile at latest time point before CAD event, participants had univariable CAD-OR = 2.27 (95% confidence interval, 1.63–3.15) and multivariable adjusted CAD-OR = 1.59 (1.09–2.30). For comparison, univariable CAD-OR for dyslipidemia, diabetes, and recent abacavir exposure were 1.58 (1.29–1.93), 2.19 (1.59–3.03), and 1.73 (1.37–2.17), respectively. Smoking and, to a lesser degree, alcohol and ethnicity attenuated the leukocyte-CAD association. Leukocytes measured up to 8 years before the event were significantly associated with CAD events.

Conclusions

PWH in Switzerland with higher leukocyte counts have an independently increased risk of CAD events, to a degree similar to traditional and HIV-related risk factors.
An unusual case of recurrence of papillary fibroelastoma: a case report
Authors: Greeshma S , Palangadan S , Leena devi K R , Vijayaraghavan G
Published: January 2023

Background

Papillary fibroelastomas (PFEs) are uncommon primary cardiac tumours and their recurrence after resection is rare.

Case summary

A 32-year-old woman, who was evaluated for recurrent embolic stroke, was found to have lesions on mitral leaflets on echocardiography. The mitral leaflets were otherwise normal with no clinical or laboratory evidence of infective endocarditis. Transthoracic, as well as transesophageal echocardiography, revealed masses on mitral leaflets, which remained almost the same over 3 years. A tentative diagnosis of PFE on the mitral valve was made. She had undergone intra-cardiac excision of mitral valve mass along with ring annuloplasty in February 2020. In November 2021, during her regular follow-up visit, transthoracic echocardiography revealed the recurrence of the masses on mitral leaflets with severe mitral regurgitation. She underwent mitral valve replacement and excision of tumour masses. Histopathological examination confirmed the diagnosis of recurrent PFE.

Discussion

Recurrence of PFEs is rare. We report a rare case of histologically proven recurrence of PFE of the mitral valve. This highlights the importance of routine post-operative echocardiographic follow-up in patients with PFE.
Widespread reticulate evolution in an adaptive radiation
Authors: DeBaun Dylan , Rabibisoa Nirhy , Raselimanana Achille P , Raxworthy Christopher J , Burbrink Frank T
Published: January 2023

A fundamental assumption of evolutionary biology is that phylogeny follows a bifurcating process. However, hybrid speciation and introgression are becoming more widely documented in many groups. Hybrid inference studies have been historically limited to small sets of taxa, while exploration of the prevalence and trends of reticulation at deep time scales remains unexplored. We study the evolutionary history of an adaptive radiation of 109 gemsnakes in Madagascar (Pseudoxyrhophiinae) to identify potential instances of introgression. Using several network inference methods, we find 12 reticulation events within the 22-million-year evolutionary history of gemsnakes, producing 28% of the diversity for the group, including one reticulation that resulted in the diversification of an 18 species radiation. These reticulations are found at nodes with high gene tree discordance and occurred among parental lineages distributed along a north-south axis that share similar ecologies. Younger hybrids occupy intermediate contact zones between the parent lineages showing that post-speciation dispersal in this group has not eroded the spatial signatures of introgression. Reticulations accumulated consistently over time, despite drops in overall speciation rates during the Pleistocene. This suggests that while bifurcating speciation rates may decline as the result of species accumulation and environmental change, speciation by hybridization may be more robust to these processes.
Dry eye in primary care: the relationship between digital display device usage and dry eye syndrome (DES) in medical students
Authors: Utlu Elif Sedanur , Bayraktar Mustafa , Utlu Bahadır
Published: January 2023

Objective

As digital display devices become more and more indispensable, associated health problems have started to increase. We aimed to investigate the frequency and relationship of digital display device usage behaviours and dry eye syndrome (DES) in medical students.

Methods

An observational, cross-sectional study was conducted on medical school students who voluntarily participated in our study online, about the duration and variety of their digital screen use, usage patterns, and protective measures, together with the Ocular Surface Disease Index (OSDI) questionnaire. Where necessary, the Schirmer-I, tear break-up time, and fluorescein staining tests were carried out.

Results

Of the 255 participants, 75.3% (n = 192) were female, 63.1% (n = 161) had no refractive vision defects, and 45.9% used smartphones for more than 5 h a day. According to the OSDI scores for DES screening, only 36.1% of the participants were normal, 17.3% had mild DES, 20.4% had moderate DES, and 26.3% had severe DES. A positive correlation was found between digital display usage time in hours per day and a high OSDI score. As the distance between the eye and the screen decreased, the DES score increased, which is significant for computer, e-book, and tablet use (P < 0.005). The DES rate of the 25 participants who underwent further evaluation was 40% for the tear break-up time test and 52% for the fluorescein staining test.

Conclusion

The high prevalence of DES due to digital screen use among medical school students highlights the importance of DES screening as a preventive measure in family medicine.
Azospirillum baldaniorum Sp 245 inoculation affects cell wall and polyamines metabolisms in cucumber seedling roots
Authors: Pereyra Cintia Mariana , Dal Lago Claudia Cristina , Creus Cecilia Mónica , Pereyra María Alejandra
Published: January 2023

Azospirillum baldaniorum Sp 245 is a model plant growth-promoting rhizobacterium. The first cross-talk with plants takes place within the roots. Roots cells growth is constrained by the primary cell wall (CW). Also, neighboring CW form the apoplast that should affect cells signaling and biochemical messages. Studies on CW phenolic composition ferulate (FA), diferulates (DFA) and p-coumarate and polyamines (PA) metabolisms of A. baldaniorum Sp 245- inoculated roots and on bacterial PA production in culture media should help to understand more about the mechanisms involved in Azospirillum-root association. For this purpose, CW-bound FA, DFA and p-coumarate contents, putrescine (put) and spermidine contents, diamine and polyamine oxidases activities, and H2O2 content of Cucumis sativus roots from dark grown seedlings inoculated with A. baldaniorum Sp 245 were determined. Also, bacterial PA production under constant agitation or static conditions was evaluated. Results showed lesser contents of all phenolics, and higher FA/DFA ratio in CW of inoculated roots that should be responsible for roots growth promotion. Also, the increased put content, DAO activity, and H2O2 production in the roots should be associated to A. baldaniorum Sp 245 growth promotion in early stages. Finally, the participation of both PA in A. baldaniorum Sp 245 biofilm formation was demonstrated.
Hypersurface curvatures of geological features
Authors: Ravve Igor , Tertois Anne-Laure , de Ribet Bruno , Koren Zvi
Published: January 2023

Reflector-normal angles and reflector-curvature parameters are the principal geometric attributes used in seismic interpretation for characterizing the orientations and shapes, respectively, of geological reflecting surfaces. Commonly, the input data set for their computation consists of fine 3-D grids of scalar fields representing either the seismic-driven reflectivities (e.g. amplitudes of 3-D seismic migrated volumes) or model-driven reflectivities, computed, for example, from the derived elastic impedance parameters. Conventionally, the computation of curvature parameters at each gridpoint is based on analysing the local change in the inline/crossline dips, considering the potential existence of a local quadratic reflecting surface in the vicinity of that point. This assumption breaks down for subsurface points in the vicinity of either complex reflecting surfaces (e.g. brittle/rough/tilted synclines/anticlines, ridges/troughs and saddles) and/or sharp, discontinuous geological features (e.g. fault edges/tips, pinch-outs, fracture systems, channels and small geobodies), where the values of the computed curvature become extremely high. However, while these high values can indicate the existence of non-reflecting objects, they do not deliver their specific geometric characteristics. In this study, we present a novel method that better characterizes the shapes of these complex geological features by extending the assumption of local surfaces (2-D surfaces in 3-D space) into local hypersurfaces (3-D hypersurfaces in 4-D space), with their corresponding (three rather than two) principal (and effective) curvature parameters. We demonstrate the advantages of our method by comparing the conventional dip-based surface curvature parameters with the hypersurface curvature parameters, using a synthetic model/image with different types and shapes of geological features and a seismic image of real data containing a complex fault and hidden buried channels.
Statistically optimal estimation of surface mass anomalies by directly using GRACE level-2 spherical harmonic coefficients as measurements
Authors: Chang Guobin , Qian Nijia , Bian Shaofeng
Published: January 2023

Point-mass inversion is widely employed in GRACE level-2 data processing. Conventionally, the spherical harmonic (SH) coefficients are used indirectly: a set of pseudo measurements is generated first using the SH coefficients through SH synthesis; then the point-mass inversion is done with these pseudo measurements. To be statistically optimal, the covariance matrix of pseudo measurements should be calculated and used to appropriately weigh the parameter estimation. In this work, we propose a statistically optimal point-mass inversion scheme by directly using the SH coefficients as measurements. We prove the equivalence between this direct approach and the conventional indirect approaches. We also demonstrated their comparable performance through both simulation and real GRACE data processing. Choosing and calculating pseudo measurements, propagating covariance matrix and potentially dealing with the singularity of the covariance matrix involved in the conventional indirect approaches are avoided in the proposed direct approach. This statistically optimal direct approach can readily be employed in mascon inversion of GRACE data and other radial basis functions-based approaches in regional gravity modeling.
Bi-allelic humanTEKT3mutations cause male infertility with oligoasthenoteratozoospermia owing to acrosomal hypoplasia and reduced progressive motility
Authors: Liu Yiyuan , Li Yuqian , Meng Lanlan , Li Kuokuo , Gao Yang , Lv Mingrong , Guo Rui , Xu Yuping , Zhou Ping , Wei Zhaolian , He Xiaojin , Cao Yunxia , Wu Huan , Tan Yueqiu , Hua Rong
Published: January 2023

Oligoasthenoteratozoospermia (OAT) can result in male infertility owing to reduced sperm motility and abnormal spermatozoan morphology. The Tektins are a family of highly conserved filamentous proteins expressed in the axoneme and associated structures in many different metazoan species. Earlier studies on mice identified Tektin3 (Tekt3) as a testis-enriched gene, and knockout of Tekt3 resulted in asthenozoospermia in the mice. Here, whole-exome sequencing of 100 males with asthenozoospermia from unrelated families was performed, followed by Sanger sequencing, leading to the identification of TEKT3 as a candidate gene in two of these patients and their associated family members. In total, three mutations in the TEKT3 gene were identified in both these patients, including one homozygous deletion–insertion mutation (c.543_547delinsTTGAT: p.Glu182*) and one compound heterozygous mutation (c.[548G > A]; [752A > C], p.[Arg183Gln]; [Gln251Pro]). Both of these mutations resulted in the complete loss of TEKT3 expression. The patients were both found to produce sperm that, although those showed no apparent defects in the flagellar structure, had reduced progressive motility. In contrast to mice, most sperm from these two patients exhibited acrosomal hypoplasia, although this did not prevent the use of the sperm for in vitro fertilization through an ICSI approach. TEKT3 was found to bind to other TEKT proteins, suggesting that these proteins form a complex within human spermatozoa. Overall, these results suggest that a loss of TEKT3 function can contribute to OAT incidence in humans. TEKT3 deficiencies can reduce sperm motility and contribute to severe acrosomal hypoplasia in spermatozoa, compromising their normal function.
Sweets and Inflammatory Bowel Disease: Patients Favor Artificial Sweeteners and Diet Foods/Drinks Over Table Sugar and Consume Less Fruits/Vegetables
Authors: Basson Abigail Raffner , Katz Jeffry , Singh Sargun , Celio Fabiano , Cominelli Fabio , Rodriguez-Palacios Alexander
Published: January 2023

Background

While artificial sweeteners are deemed safe, preclinical studies indicate that artificial sweeteners contribute to gastrointestinal inflammation. Little is known about patients’ perceptions and consumption of artificial sweeteners in inflammatory bowel disease (IBD). We surveyed the consumption frequency and beliefs of IBD patients and control participants regarding artificial sweeteners.

Methods

We surveyed 130 individuals (IBD patients, n = 93; control/non-IBD participants, n = 37) among our tertiary hospital population to determine consumption frequency and beliefs regarding artificial sweeteners (Splenda/sucralose, Stevia/stevia, NutraSweet/Equal/aspartame). A 14-question questionnaire surveyed the frequency of 9 dietary habits, preferences, and beliefs on health benefits of commercial artificial sweeteners, using the following as positive and negative control questions: table sugar, water, fruits/vegetables, and coconut-oil, among others.

Results

Despite the similarity in yes/no consumption data, artificial sweeteners (Q4 t test P = .023) and diet (low calorie) foods/drinks (Q4 t test P = .023) were consumed more frequently by patients with IBD than by control participants, while no difference in preference for water instead of juices/sodas was observed between IBD patients and control participants. Conversely, patients with IBD consumed table sugar less frequently than control participants (Q1 t test-P = .09), in agreement with their reporting of sugary foods as cause of symptoms (P < .01). A positive correlation was observed between artificial sweeteners and fresh fruits/vegetables among the first 31 IBD patients (Spearman P = .017) and confirmed with 62 new IBD patients (r = 0.232; 95% CI, 0.02-0.43; P = .031), indicating that artificial sweeteners are deemed a healthy habit in IBD. Excluding fresh fruits/vegetables, multivariate analyses to develop surrogate principal component analysis indexes of healthy habits confirmed that artificial sweeteners consumption follows healthy preferences among our IBD patients (adjusted P < .0001).

Conclusions

Consumption of artificial sweeteners correlated with healthy habits, suggesting that our IBD population deemed artificial sweeteners as healthy and/or had preferences for naturally or artificially sweetened flavors and products.
Downstream foreign MNEs and local suppliers’ innovation in a dynamic environment: the moderating effect of network diversity
Authors: Ha Yoo Jung
Published: January 2023

This study investigates how the presence of foreign multinational enterprises (MNEs) in downstream sectors influences innovation in upstream local suppliers via backward linkages. Analysis using Korean Innovation Surveys shows backward linkages of foreign MNEs to have negative effects on local suppliers. While local suppliers operating in dynamic environments can avert negative effects, those locked in extant innovation networks continue to experience adverse effects. Our findings show that the effect of MNE presence on local firms should be evaluated in conjunction with given industrial changes and heterogeneous firm strategies.
Phenomenological analysis of simple ion channel block in large populations of uncoupled cardiomyocytes
Authors: Simitev Radostin D , Al Dawoud Antesar , Aziz Muhamad H N , Myles Rachel , Smith Godfrey L
Published: January 2023

Current understanding of arrhythmia mechanisms and design of anti-arrhythmic drug therapies hinges on the assumption that myocytes from the same region of a single heart have similar, if not identical, action potential waveforms and drug responses. On the contrary, recent experiments reveal significant heterogeneity in uncoupled healthy myocytes both from different hearts as well as from identical regions within a single heart. In this work, a methodology is developed for quantifying the individual electrophysiological properties of large numbers of uncoupled cardiomyocytes under ion channel block in terms of the parameters values of a conceptual fast-slow model of electrical excitability. The approach is applied to a population of nearly 500 rabbit ventricular myocytes for which action potential duration (APD) before and after the application of the drug nifedipine was experimentally measured (Lachaud et al., 2022, Cardiovasc. Res.). To this end, drug action is represented by a multiplicative factor to an effective ion conductance, a closed form asymptotic expression for APD is derived and inverted to determine model parameters as functions of APD and $\varDelta $APD (drug-induced change in APD) for each myocyte. Two free protocol-related quantities are calibrated to experiment using an adaptive-domain procedure based on an original assumption of optimal excitability. The explicit APD expression and the resulting set of model parameter values allow (a) direct evaluation of conditions necessary to maintain fixed APD or $\varDelta $APD, (b) predictions of the proportion of cells remaining excitable after drug application, (c) predictions of stimulus period dependency and (d) predictions of dose-response curves, the latter being in agreement with additional experimental data.
Low regularity exponential-type integrators for the “good” Boussinesq equation
Authors: Li Hang , Su Chunmei
Published: January 2023

In this paper, two semidiscrete low regularity exponential-type integrators are proposed and analyzed for the “good” Boussinesq equation, including a first-order integrator and a second-order one. Compared to the existing numerical methods, the convergence rate can be achieved under weaker regularity assumptions on the exact solution. Specifically, the first-order integrator is convergent linearly in $H^r$ for solutions in $H^{r+1}$ if $r>1/2$, i.e., the boundedness of one additional derivative of the solution is required to achieve the first-order convergence. When $r>7/6$, we can even prove linear convergence in $H^r$ for solutions in $H^{r+2/3}$. What’s more, half-order convergence is established in $H^{r}(r>3/2)$ for any solutions in $H^r$, i.e., no additional smoothness assumptions are needed. For the second-order integrator, the quadratic convergence in $H^{r}$$(r>1/2)$ (or $L^2$) is demonstrated, when the solutions belong to $H^{r+2}$ (or $H^{9/4}$). Numerical examples illustrating the convergence analysis are included. A comparison with other methods demonstrates the superiority of the newly proposed exponential-type integrators for rough data.
Adaptive sampling strategies for risk-averse stochastic optimization with constraints
Authors: Beiser Florian , Keith Brendan , Urbainczyk Simon , Wohlmuth Barbara
Published: January 2023

We introduce adaptive sampling methods for stochastic programs with deterministic constraints. First, we propose and analyze a variant of the stochastic projected gradient method, where the sample size used to approximate the reduced gradient is determined on-the-fly and updated adaptively. This method is applicable to a broad class of expectation-based risk measures, and leads to a significant reduction in the individual gradient evaluations used to estimate the objective function gradient. Numerical experiments with expected risk minimization and conditional value-at-risk minimization support this conclusion, and demonstrate practical performance and efficacy for both risk-neutral and risk-averse problems. Second, we propose an SQP-type method based on similar adaptive sampling principles. The benefits of this method are demonstrated in a simplified engineering design application, featuring risk-averse shape optimization of a steel shell structure subject to uncertain loading conditions and model uncertainty.
Mapping of structural arrangement of cells and collective calcium transients: an integrated framework combining live cell imaging using confocal microscopy and UMAP-assisted HDBSCAN-based approach
Authors: Gare Suman , Chel Soumita , Abhinav T K , Dhyani Vaibhav , Jana Soumya , Giri Lopamudra
Published: January 2023

Live cell calcium (Ca2+) imaging is one of the important tools to record cellular activity during in vitro and in vivo preclinical studies. Specially, high-resolution microscopy can provide valuable dynamic information at the single cell level. One of the major challenges in the implementation of such imaging schemes is to extract quantitative information in the presence of significant heterogeneity in Ca2+ responses attained due to variation in structural arrangement and drug distribution. To fill this gap, we propose time-lapse imaging using spinning disk confocal microscopy and machine learning-enabled framework for automated grouping of Ca2+ spiking patterns. Time series analysis is performed to correlate the drug induced cellular responses to self-assembly pattern present in multicellular systems. The framework is designed to reduce the large-scale dynamic responses using uniform manifold approximation and projection (UMAP). In particular, we propose the suitability of hierarchical DBSCAN (HDBSCAN) in view of reduced number of hyperparameters. We find UMAP-assisted HDBSCAN outperforms existing approaches in terms of clustering accuracy in segregation of Ca2+ spiking patterns. One of the novelties includes the application of non-linear dimension reduction in segregation of the Ca2+ transients with statistical similarity. The proposed pipeline for automation was also proved to be a reproducible and fast method with minimal user input. The algorithm was used to quantify the effect of cellular arrangement and stimulus level on collective Ca2+ responses induced by GPCR targeting drug. The analysis revealed a significant increase in subpopulation containing sustained oscillation corresponding to higher packing density. In contrast to traditional measurement of rise time and decay ratio from Ca2+ transients, the proposed pipeline was used to classify the complex patterns with longer duration and cluster-wise model fitting. The two-step process has a potential implication in deciphering biophysical mechanisms underlying the Ca2+ oscillations in context of structural arrangement between cells.
Histology of Convergent Probing Appendages in Mormyridae
Authors: Peterson R D , Evans A J , Hernandez L P
Published: January 2023

Synopsis

Mormyridae is an early diverging family of Teleostean fishes that produce an electric field for navigation and communication using an electric organ. This clade has a diverse array of soft-tissue rostral appendages, such as the chin-swelling, the Schnauzenorgan, and the tubesnout combined with a Schnauzenorgan, that have evolved multiple times. Here we assess if macroscopically convergent, soft-tissue rostral appendages are also histologically convergent. Further, we investigate how the histology of these appendages can inform their function. We sampled independent gains of the chin-swelling and Schnauzenorgan to understand similarities and differences in their anatomies. We show that macroscopically convergent rostral appendages are also convergent at a histological level, and different types of rostral appendages share a similar anatomy; that said, minor differences likely relate to their specific functions. Based on a comparison of the skeletal muscle distribution and the differing attachment shapes of each appendage to the dentary, we conclude that the Schnauzenorgan is capable of a wider range of movements than the chin swelling. Furthermore, the anatomy suggests that these soft-tissue rostral appendages likely function as electrosensory foveas (i.e., an appendage that focuses a sensory system). Lastly, these histological data support the hypothesis that the chin swelling may be a precursor to the Schnauzenorgan.
Jaw1/LRMP is associated with the maintenance of Golgi ribbon structure
Authors: Okumura Wataru , Tadahira Kazuko , Kozono Takuma , Tamura-Nakano Miwa , Sato Hiroyuki , Matsui Hitomi , Dohi Taeko , Rohrer Jack , Tonozuka Takashi , Nishikawa Atsushi
Published: January 2023

Jaw1/LRMP is a membrane protein that is localized to the endoplasmic reticulum and outer nuclear membrane. Previously, we revealed that Jaw1 functions to maintain nuclear shape by interacting with microtubules as a Klarsicht/ANC-1/Syne/homology (KASH) protein. The loss of several KASH proteins causes defects in the position and shape of the Golgi apparatus as well as the nucleus, but the effects of Jaw1 depletion on the Golgi apparatus were poorly understood. Here, we found that siRNA-mediated Jaw1 depletion causes Golgi fragmentation with disordered ribbon structure in the melanoma cell, accompanied by the change in the localization of the Golgi-derived microtubule network. Thus, we suggest that Jaw1 is a novel protein to maintain the Golgi ribbon structure, associated with the microtubule network.
How Verb Tense Shapes Persuasion
Authors: Packard Grant , Berger Jonah , Boghrati Reihane
Published: January 2023

When sharing information and opinions about products, services, and experiences, communicators often use either past or present tense (e.g., “That restaurant was great” or “That restaurant is great”). Might such differences in verb tense shape communication’s impact, and if so, how? A multimethod investigation, including eight studies conducted in the field and lab, demonstrates that using present (vs. past) tense can increase persuasion. Natural language processing of over 500,000 online reviews in multiple product and service domains, for example, illustrates that reviews that use more present tense are seen as more helpful and useful. Follow-up experiments demonstrate that shifting from past to present tense increases persuasion and illustrate the underlying process through both mediation and moderation. When communicators use present (rather than past) tense to express their opinions and experiences, it suggests that they are more certain about what they are saying, which increases persuasion. These findings shed light on how language impacts consumer behavior, highlight how a subtle, yet central linguistic feature shapes communication, and have clear implications for persuasion across a range of situations.