bluuebunny/crossref_metadata_2025 huggingface dataset:
A niching particle swarm optimization strategy for the multimodal inversion of surface waves
Authors: Zhang Kai , Li Hongyi , Wang Kai , Liu Min , Cai Wei , Liu Dongming
Published: October 2022

In practice, near-surface structures with shear wave velocity inversions or strong shear wave velocity contrasts may cause the phase velocity spectra of surface waves to be complex. Hence, it is sometimes difficult to identify mode numbers in the phase velocity spectrum. To avoid numbering different modes, the determinant misfit function has been applied to invert multimodal dispersion curves with a very limited computational cost due to the absence of the root-seeking procedure. However, this function presents a complicated relation with modal parameters and thus has multiple minima, resulting in an increase in model ambiguity. Therefore, it is more appropriate to adopt a multimodal optimization algorithm to find multiple minima instead of obtaining one optimal solution. In this study, we use a niching particle swarm optimization to find multiple minima with an enhanced fine search ability. Subsequently, we performed cluster analysis to distinguish different clusters in the inverted solutions and find the best-fitting profiles from multiple minima based on the Euclidean distance between the measured and inverted dispersion curves. Moreover, a modified Thomson–Haskell transfer matrix method is used to calculate the determinant misfit function for a better constraint on inversion because it can only resolve the surface wave modes possessing energy at the free surface, where both the sources and geophones are commonly deployed for active and passive surface wave exploration. Tests of synthetic and field data demonstrate that our inversion method is both effective and robust and emphasize its great potential in urban subsurface exploration and geotechnical characterization applications.
The importance of side branches of glycosylphosphatidylinositol anchors: a molecular dynamics perspective
Authors: Banerjee Pallavi , Silva Daniel Varon , Lipowsky Reinhard , Santer Mark
Published: October 2022

Many proteins are anchored to the cell surface of eukaryotes using a unique family of glycolipids called glycosylphosphatidylinositol (GPI) anchors. These glycolipids also exist without a covalently bound protein, in particular on the cell surfaces of protozoan parasites where they are densely populated. GPIs and GPI-anchored proteins participate in multiple cellular processes such as signal transduction, cell adhesion, protein trafficking and pathogenesis of Malaria, Toxoplasmosis, Trypanosomiasis and prion diseases, among others. All GPIs share a common conserved glycan core modified in a cell-dependent manner with additional side glycans or phosphoethanolamine residues. Here, we use atomistic molecular dynamic simulations and perform a systematic study to evaluate the structural properties of GPIs with different side chains inserted in lipid bilayers. Our results show a flop-down orientation of GPIs with respect to the membrane surface and the presentation of the side chain residues to the solvent. This finding agrees well with experiments showing the role of the side residues as active epitopes for recognition of GPIs by macrophages and induction of GPI-glycan-specific immune responses. Protein-GPI interactions were investigated by attaching parasitic GPIs to Green Fluorescent Protein. GPIs are observed to recline on the membrane surface and pull down the attached protein close to the membrane facilitating mutual contacts between protein, GPI and the lipid bilayer. This model is efficient in evaluating the interaction of GPIs and GPI-anchored proteins with membranes and can be extended to study other parasitic GPIs and proteins and develop GPI-based immunoprophylaxis to treat infectious diseases.
Stable isotopes reveal that bottom-up omnivory drives food chain length and trophic position in eutrophic coastal ecosystems
Authors: Lerner Jacob E , Marchese Christian , Hunt Brian P V
Published: October 2022

In coastal marine food webs, food chain length and the distribution of trophic levels mediate the impacts of emerging threats such as overfishing, pollution, and climate change, through their effect on essential properties such as productivity, connectivity, and energy transfer efficiency. These two components of food web structure are therefore an essential element of ecosystem-based management; however, what drives them remains poorly understood. It has been hypothesized that high primary production drives lower trophic levels and shorter food chain length in coastal regions. Here, we evaluate this hypothesis on the British Columbia (BC) coast as this coastal marine ecosystem is comprised of regions with contrasting levels of primary production. We measured nitrogen stable isotopes from zooplankton, micronekton, and nekton collected from four of the main water bodies of southern BC during a survey completed in August of 2019. We used Sentinel-3 satellite data to determine overall production in each region across a 5-year climatology and during the 2019 season. Results showed that primary production varied significantly between the four regions and that increases in phytoplankton biomass were driven by increases in microphytoplankton. Nitrogen isotope data demonstrated a significant inverse relationship between a region’s primary production and both total food chain length and trophic level in species sampled in multiple regions, but no change in the trophic structure of the zooplankton community across regions. Changes in species’ trophic levels were therefore driven by shifts in the level of zooplanktivory. These results support a model of bottom-up omnivory driving coastal food web structure, where levels of primary production, specifically biomass of microphytoplankton, determine food chain length and the distribution of trophic levels. High microphytoplankton biomass supports a large biomass of large grazing zooplankton, which drive increases in omnivorous feeding behaviour among the micronekton and nekton.
Primary Anal Cancer Screening Results From 381 Women With Human Immunodeficiency Virus
Authors: Liu Yuxin , Weiss Kevin , Zamudio Andrés Ramírez , Hayes Monica Prasad , Saleh Mona , Gaisa Michael M , Sigel Keith
Published: October 2022

Background

Women with human immunodeficiency virus (WWH) have an elevated risk for human papillomavirus (HPV)-associated anal cancer. Primary anal cancer screening results from this population could inform practice guidelines.

Methods

In total, 381 WWH with anal cytology screening, high-risk HPV (hrHPV) testing and genital (cervical or vaginal) cotesting within 6 months were identified during 2012–2019. Those with anal cytology of atypical squamous cells of undetermined significance (ASCUS) or worse underwent high-resolution anoscopy and biopsy. Independent predictors of anal hrHPV, HPV16, and histological anal high-grade squamous intraepithelial lesions (aHSIL) were identified using adjusted logistic regression models.

Results

Prevalence of anal hrHPV, HPV16, and ASCUS or worse cytology was 61%, 13%, and 68%. Histological aHSIL was detected in 42% of WWH with ASCUS or worse anal cytology. Prevalence of genital hrHPV, HPV16, and ASCUS or worse cytology was 30%, 4%, and 28%. Genital hrHPV predicted anal hrHPV (odds ratio [OR], 5.05), while genital HPV16 predicted anal HPV16 (OR, 9.52). Genital hrHPV and anal HPV16 predicted histological aHSIL (ORs, 2.78 and 10.9).

Conclusions

Anal HPV disease was highly prevalent in this primary screening cohort of WWH. While genital screening results predicted anal disease, rates of isolated anal HPV disease were substantial, supporting universal anal cancer screening for this population.
A regional approach to reduce postoperative opioid prescribing in Ontario, Canada
Authors: Jackson Timothy D , Maeda Azusa , Beath Tricia , Ahmad Nancy , Price-arsenault Pierrette , Jia Hui , Lam Jonathan , Schramm David
Published: October 2022

Background: Opioid-related morbidity and mortality continue to rise in the province of Ontario. We implemented a provincial campaign to reduce the number of opioid pills prescribed at discharge after surgery in the Ontario Surgical Quality Improvement Network (ON-SQIN).

Methods: Activities related to the provincial campaign were implemented between April 2019 and March 2020 and between October 2020 and March 2021. Self-reported data from participating hospitals were used to determine changes in postoperative opioid prescribing patterns across participating hospitals.

Results: A total of 33 and 26 hospitals participated in the provincial campaign in the first and second year, respectively. During the first year of the campaign, the median morphine equivalent (MEQ) from opioid prescriptions decreased significantly in a number of surgical specialties, including General Surgery (from 105 [75–130] to 75 [55–107], P < 0.001) (median, interquartile range) and Orthopedic Surgery (from 450 [239–600] to 334 [167–435], P < 0.001). The median number of opioid pills prescribed at discharge per surgery also decreased significantly, from 25 (15–53) to 15 (11–38) for 1 mg hydromorphone (P < 0.001) and 25 (20–51) to 20 (15–30) for oxycodone (P < 0.001). The decrease in opioid prescriptions continued in the second year of the campaign.

Conclusions: Our approach resulted in a significant reduction in the number of postoperative opioids prescribed across a number of surgical specialties. Our findings indicate that evidence-based strategies derived from a regional collaborative network can be leveraged to promote and sustain quality improvement activities.
Taxonomic boundaries in Lesser Treeshrews (Scandentia, Tupaiidae: Tupaia minor)
Authors: Juman Maya M , Woodman Neal , Miller-Murthy Ananth , Olson Link E , Sargis Eric J
Published: October 2022

The Lesser Treeshrew, Tupaia minorGünther, 1876, is a small mammal from Southeast Asia with four currently recognized subspecies: T. m. minor from Borneo; T. m. malaccana from the Malay Peninsula; T. m. humeralis from Sumatra; and T. m. sincepis from Singkep Island and Lingga Island. A fifth subspecies, T. m. caedis, was previously synonymized with T. m. minor; it was thought to occur in northern Borneo and on the nearby islands of Banggi and Balambangan. These subspecies were originally differentiated based on pelage color, a plastic feature that has proven to be an unreliable indicator of taxonomic boundaries in treeshrews and other mammals. To explore infraspecific variation among T. minor populations across the Malay Peninsula, Borneo, Sumatra, and smaller islands, we conducted multivariate analyses of morphometric data collected from the hands and skulls of museum specimens. Principal component and discriminant function analyses reveal limited differentiation in manus and skull proportions among populations of T. minor from different islands. We find no morphometric support for the recognition of the four allopatric subspecies and no support for the recognition of T. m. caedis as a separate subspecies on Borneo.
Jasmonate-based warfare between the pathogenic intruder and host plant: who wins?
Authors: Li Rui , Yang Yongfang , Lou Hao , Wang Weicheng , Yan Jianbin , Shan Xiaoyi , Xie Daoxin
Published: October 2022

Plants and microbial pathogens often engage in a fierce war that determines their survival. Host plants have evolved sophisticated regulatory mechanisms to fine-tune defense responses to counter attacks from pathogens, while pathogens often hijack the lipid-derived phytohormone jasmonate to cause hormonal signaling imbalances for efficient infection. This review focuses on the jasmonate-based warfare between host plants and pathogenic intruders, and further discusses approaches to uncouple plant growth and defense tradeoffs in crop breeding.
A refined dynamical mass for the black hole in the X-ray transient XTE J1859+226
Authors: Yanes-Rizo I V , Torres M A P , Casares J , Motta S E , Muñoz-Darias T , Rodríguez-Gil P , Armas Padilla M , Jiménez-Ibarra F , Jonker P G , Corral-Santana J M , Fender R
Published: October 2022

We present two contiguous nights of simultaneous time-resolved Gran Telescopio Canarias spectroscopy and William Herschel Telescope photometry of the black hole X-ray transient XTE J1859+226, obtained in 2017 July during quiescence. Cross-correlation of the individual spectra against a late K-type spectral template enabled us to constrain the orbital period to 0.276 ± 0.003 d and the radial velocity semi-amplitude of the donor star to K2 = 550 ± 59 km s−1. An ellipsoidal modulation is detected in the photometric r- and i-band light curves, although it is strongly contaminated by flickering activity. By exploiting correlations between the properties of the double-peaked H α emission-line profile and the binary parameters, we derived an orbital inclination of 66.6 ± 4.3 deg, a refined K2 = 562 ± 40 km s−1 and mass ratio q = M2/M1 = 0.07 ± 0.01. From these values, we obtained an updated black hole mass of M1 = 7.8 ± 1.9 M⊙. An independent mass estimate based on X-ray timing agrees well with our value, which gives further support for the outburst quasi-periodic oscillation triplet being explained by the relativistic precession model. We also obtained a companion star mass M2 = 0.55 ± 0.16 M⊙, which is consistent with its K5-K7 V spectral type.
Is binning always sinning? The impact of time-averaging for exoplanet phase curves
Authors: Morello Giuseppe , Dyrek Achrène , Changeat Quentin
Published: October 2022

We explore how finite integration time or temporal binning can affect the analysis of exoplanet phase curves. We provide analytical formulae to account for this effect or, if neglected, to estimate the potential biases in the retrieved parameters. As expected, due to their smoother variations over longer time-scales, phase curves can be binned more heavily than transits without causing severe biases. In the simplest case of a sinusoidal phase curve with period P, the integration time Δt reduces its amplitude by the scaling factor sinc(πΔt/P), without altering its phase or shape. We also provide formulae to predict reasonable parameter error bars from phase-curve observations. Our findings are tested with both synthetic and real data sets, including unmodelled astrophysical signals and/or instrumental systematic effects. Tests with the Spitzer data show that binning can affect the best-fitting parameters beyond predictions, due to the correction of high-frequency correlated noise. Finally, we summarize key guidelines for speeding up the analysis of exoplanet phase curves without introducing significant biases in the retrieved parameters.
Efficacy and safety of the anti-TNF multivalent NANOBODY® compound ozoralizumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: A 52-week result of a Phase II/III study (OHZORA trial)
Authors: Tanaka Yoshiya , Kawanishi Masafumi , Nakanishi Megumi , Yamasaki Hironori , Takeuchi Tsutomu
Published: October 2022

Objective

To assess the efficacy and safety through a 52-week treatment with subcutaneous ozoralizumab at 30 or 80 mg in patients with active rheumatoid arthritis despite methotrexate therapy.

Methods

This multicentre, randomized, placebo-controlled, double-blind, parallel-group confirmatory trial included a 24-week double-blind treatment period followed by a 28-week open-label treatment period. The double-blind treatment period randomized 381 (2:2:1) patients to placebo and ozoralizumab at 30 or 80 mg, and patients receiving placebo were re-randomized (1:1) to ozoralizumab at 30 or 80 mg in the open-label period.

Results

The ozoralizumab groups showed good clinical improvement, with high American College of Rheumatology response rates at 52 weeks, as well as good improvements in other endpoints, which were observed from Day 3 and maintained through Week 52. Furthermore, the ozoralizumab groups showed a high remission rate in clinical and functional remission at Week 52. Serious adverse events occurred in a total of 23 patients in the ozoralizumab groups, without differences in incidence between doses.

Conclusions

Ozoralizumab demonstrated significant therapeutic effects and efficacy, which was maintained for 52 weeks. The safety profile was consistent with the evaluated results in interim analysis at Week 24, and ozoralizumab was well-tolerated up to Week 52.
Vitamin D status-associated postoperative complications in patients with hip dysplasia after periacetabular osteotomy: A case–control study
Authors: Kitade Kazuki , Mawatari Taro , Baba Shoji , Sueda Reima , Hagio Satoshi , Kawahara Shinya , Ikemura Satoshi , Nakashima Yasuharu
Published: October 2022

Objectives

This study aimed to clarify the relationship between vitamin D status and complications after periacetabular osteotomy.

Methods

A total of 46 hips of 39 patients (3 men and 36 women; mean age at surgery, 41.0 years; mean postoperative follow-up duration, 63 months) were reviewed to obtain the following information: patients’ serum 25-hydroxyvitamin D [25(OH)D] status, prevalence of postoperative delayed union of osteotomy sites in the greater trochanter (DUGT) and ischiopubic stress fractures (IPSFs), and risk factors.

Results

The mean serum 25(OH)D level was 11.9 ng/ml. DUGT and IPSF were found in four (10.3%) and three (7.7%) patients, respectively. Serum 25(OH)D levels ≤ 11 ng/ml were significantly associated with DUGT in female patients (p = .02). Serum 25(OH)D levels ≤ 9 ng/ml and smoking were significantly associated with IPSF (p = 0.01 and 0.02, respectively). Overall, 21.7% of patients with serum 25(OH)D levels ≤ 11 ng/ml developed at least one complication; no complications occurred when serum 25(OH)D levels were >11 ng/ml.

Conclusion

Severe vitamin D deficiency was highly prevalent in relatively young patients. Vitamin D deficiency and smoking were independent risk factors for postoperative complications. Proactive supplementation is advisable to reduce postoperative complications, especially in patients with serum 25(OH)D levels ≤ 11 ng/ml.
Carbon fixation pathways across the bacterial and archaeal tree of life
Authors: Garritano Alessandro N , Song Weizhi , Thomas Torsten
Published: October 2022

Carbon fixation is a critical process for our planet; however, its distribution across the bacterial and archaeal domains of life has not been comprehensively studied. Here, we performed an analysis of 52,515 metagenome-assembled genomes and discover carbon fixation pathways in 1,007 bacteria and archaea. We reveal the genomic potential for carbon fixation through the reverse tricarboxylic acid cycle in previously unrecognized archaeal and bacterial phyla (i.e. Thermoplasmatota and Elusimicrobiota) and show that the 3-hydroxypropionate bi-cycle is not, as previously thought, restricted to the phylum Chloroflexota. The data also substantially expand the phylogenetic breadth for autotrophy through the dicarboxylate/4-hydroxybutyrate cycle and the Calvin–Benson–Bassham cycle. Finally, the genomic potential for carbon fixation through the 3-hydroxypropionate/4-hydroxybutyrate cycle, previously exclusively found in Archaea, was also detected in the Bacteria. Carbon fixation thus appears to be much more widespread than previously known, and this study lays the foundation to better understand the role of archaea and bacteria in global primary production and how they contribute to microbial carbon sinks.
State of the Field of Plant Pathogen Diagnostic Assay Development and Validation
Authors: Sharma Poonam , Luster Douglas G.
Published: October 2022

Diagnostic assays for plant pathogens are a critical component in the surveillance, detection, and management of disease in the production of food, feed, and fiber. Producers, crop consultants, and state and federal officials depend on rapid and accurate diagnostics for response, disease mitigation, crop management, and regulatory decisions affecting trade and export prices. Diagnostic assays undergoing development must be validated to understand how well the assay will perform on given sample matrices, in different user hands, and under varying laboratory conditions before deployment and application in diagnostic clinics and distribution as commercially available assays. The validation of diagnostic assays is a time-consuming, expensive, multitiered process, requiring pathogen and near neighbor reference materials, barcode and/or genome sequence data, and cross-laboratory partnerships. Regulatory agencies and diagnostic clinics do not often have fully validated assays to deploy during an outbreak of a novel pathogen. Our survey of recent publications describing the development of diagnostics for plant pathogens found that those detailing an appropriate and robust diagnostic assay validation process were few in number. The results point out the need for broad application of standards and rigor in the conception, development, and execution of diagnostic assay validation.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Vindoline ameliorates intestinal barrier damage in Crohn's disease mice through MAPK signaling pathway
Authors: Zhang Xiaofeng , Zuo Lugen , Geng Zhijun , Song Xue , Li Jing , Ge Sitang , Jiang Yifan , Yang Zi , Liu Guangyong , Zhao Yajing , Zhao Hao , Yu Liang , Hu Jianguo
Published: October 2022

Intestinal inflammation and intestinal barrier damage are important pathological changes in Crohn's disease (CD). Vindoline is a natural monomer with anti‐inflammatory effects. We employed CD model mice to explore the effect of Vindoline on CD‐like colitis and the possible mechanism. Il‐10‐deficient (Il‐10−/−) mice and wild‐type (WT) mice (both aged 15 weeks, male) were used to explore the effect of Vindoline on colitis and intestinal barrier damage, as well as macrophage‐mediated inflammation. Bone‐marrow‐derived macrophages (BMDMs) and colonic organoids from mice were used to explore the inhibitory effect of Vindoline on macrophage‐mediated inflammation and the protective effect on inflammation‐induced intestinal barrier damage as well as the possible mechanism. We found that Vindoline significantly ameliorated colitis in CD mice, as evidenced by increased weight change and colon length and decreased the colon macroscopic injury score, histological inflammatory score, and the expression of pro‐inflammatory mediators. Vindoline also protected against intestinal barrier damage in CD mice. Furthermore, Vindoline inhibited macrophage‐mediated inflammation and protected against inflammation‐induced intestinal barrier damage in the coculture system. In addition, Vindoline ameliorated colitis in CD mice by protecting against inflammation‐induced intestinal barrier damage, which may be caused by inhibition of MAPK signaling pathway. This protective effect suggests that Vindoline has potential value for clinical application in the treatment of CD.
Long-term Use of Wearable Health Technology by Chronic Pain Patients
Authors: Han John J. , Graham Jove H. , Snyder Dawn I. , Alfieri Thomas
Published: October 2022

Objectives:

People living with chronic pain may use wearable health technology (WHT) in conjunction with an expert-directed pain management program for up to 1 year. WHT use may be associated with improvements in key patient outcomes.

Methods:

A 12-month study of WHT use among people with chronic pain was conducted, consisting of iPhone and Apple Watch applications to measure movement, sleep, and self-reported pain. Clinical outcomes among 105 patients enrolled in a multidisciplinary pain program that included WHT use were compared with 146 patients in the same program but without WHT, and to 161 patients receiving medical pain management without WHT.

Results:

Participants used the WHT on average 143.0 (SD: 117.6) out of 365 days. Mixed-effects models revealed participants who used WHT had decreases in depression scores (−7.83, P<0.01) and prescribed morphine milligram equivalents (−21.55, P=0.04) over 1 year. Control groups also showed decreases in depression scores (−5.08, P=0.01; −5.68, P<0.01) and morphine milligram equivalents (−18.67, P=0.01; −10.99, ns). The estimated slope of change among the WHT was not statistically different than control groups.

Discussion:

Patients who used WHT as part of their pain management program demonstrated a willingness to do so for extended periods of time despite living with chronic pain and other comorbidities. Data trends suggest that WHT use may positively impact depression and prescribed medication. Additional research is warranted to investigate the potential of WHT to improve the negative consequences of chronic pain.
SARS-CoV-2: Has artificial intelligence stood the test of time
Authors: Sajid Mir Ibrahim , Ahmed Shaheer , Waqar Usama , Tariq Javeria , Chundrigarh Mohsin , Balouch Samira Shabbir , Abaidullah Sajid
Published: October 2022

Artificial intelligence (AI) has proven time and time again to be a game-changer innovation in every walk of life, including medicine. Introduced by Dr. Gunn in 1976 to accurately diagnose acute abdominal pain and list potential differentials, AI has since come a long way. In particular, AI has been aiding in radiological diagnoses with good sensitivity and specificity by using machine learning algorithms. With the coronavirus disease 2019 pandemic, AI has proven to be more than just a tool to facilitate healthcare workers in decision making and limiting physician-patient contact during the pandemic. It has guided governments and key policymakers in formulating and implementing laws, such as lockdowns and travel restrictions, to curb the spread of this viral disease. This has been made possible by the use of social media to map severe acute respiratory syndrome coronavirus 2 hotspots, laying the basis of the “smart lockdown” strategy that has been adopted globally. However, these benefits might be accompanied with concerns regarding privacy and unconsented surveillance, necessitating authorities to develop sincere and ethical government–public relations.
Disseminated Mucocutaneous Histoplasmosis Diagnosed in the United Kingdom, Presumably as a Result of Recrudescence Decades After Primary Infection Following Immunosuppressive Treatment of Its Mimic, Sarcoidosis: A Multidisciplinary Cautionary Tale
Authors: Earp Eleanor , Gordon Patricia M. , Tan Adrian , Page Iain , Thum Chee K. , Mackenzie Andrew I. , Johnson Elizabeth , Biswas Asok
Published: October 2022

Histoplasmosis is a dimorphic fungal infection, which is rare outside endemic pockets in North, Central, and South America, Asia, and Africa. Herein, we describe a woman in her 80s living in the Scottish Borders region of the United Kingdom with a recent diagnosis of granulomatous rosacea, who on receiving escalating immunosuppression for suspected sarcoidosis, and long-standing rheumatoid arthritis developed a striking eruption involving her eyelids along with painful ulceration of the oral and nasal mucosa. Histopathologic examination of the skin and mucosal lesions demonstrated granulomatous inflammation with numerous yeast forms of fungal organisms with morphological characteristics of Histoplasma species. This was confirmed to be H. capsulatum on fungal culture and direct panfungal polymerase chain reaction assay. Although the patient had not left the United Kingdom for more than 20 years, she gave a travel history involving multiple trips to countries where histoplasmosis is known to occur, before that. This case exemplifies the challenges involved in making a diagnosis of histoplasmosis in nonendemic regions for both clinicians and pathologists alike. In this particular patient, the diagnostic difficulties were compounded by the clinicopathological overlap with other cutaneous and systemic granulomatous disorders like granulomatous rosacea and suspected sarcoidosis and also the exceptionally long latency period between the purported historical primary infection and recent recrudescence. We highlight this unusual case to increase an awareness of histoplasmosis, which is very rare in nonendemic regions like the United Kingdom and involves cases acquired during residence in or travel to endemic areas, to ensure its prompt recognition and treatment.
Use of Cytokeratin 17 in the Differentiation Between Desmoplastic Trichilemmoma and Cutaneous Basal Cell Carcinoma
Authors: Chaudet Kristine M. , Stagner Anna M. , Nazarian Rosalynn M.
Published: October 2022

Desmoplastic trichilemmoma (DTL) is a variant of trichilemmoma characterized by a prominent desmoplastic stroma that may mimic invasive carcinoma. These lesions typically show features of a conventional trichilemmoma at the periphery, surrounding dense hyalinized stroma with entrapped cords of tumor cells. On a small or superficial biopsy, DTL may pose a diagnostic challenge in distinguishing this benign adnexal neoplasm from invasive carcinoma, particularly basal cell carcinoma (BCC). We aimed to investigate whether the immunohistochemical expression of cytokeratin 17 (CK17) would be useful in the differentiation between DTL and BCC. CK17 is expressed in normal adnexal structures and has been shown to demonstrate strong staining in BCCs. Expression of CK17 was examined in 23 cases of DTL and 23 BCCs. An immunoreactivity score was assigned using the percentage of tumor cells staining with scoring as follows: 0, complete negativity; 1, < 15% tumor cells staining; 2, 15%–84% tumor cells staining; and 3, >85% staining. All cases of BCC scored as 3, whereas 18% of DTL scored as 3. The mean percent staining for CK17 was significantly higher for BCCs (97% of tumor cells) than DTLs (57% of tumor cells); P < 0.001 in the unpaired t test. The pattern of CK17 staining may also help differentiate between cases scoring 3. All BCCs showed strong diffuse staining throughout, whereas for those cases of DTL with a score of 3, the peripheral basaloid rim in the tumor lobules did not stain. CK17 is a useful adjunct in distinguishing DTL from BCC in small or superficial biopsy specimens.
IL-17 Expression in the Perifollicular Fibrosis in Biopsies From Lichen Planopilaris
Authors: Miteva Mariya , Nadji Mehrdad , Billero Victoria , LaSenna Charlotte , Nattkemper Leigh , Romanelli Paolo
Published: October 2022

Background:

Lichen planopilaris (LPP) is a primary lymphocytic cicatricial alopecia for which therapy is often ineffective and there is no cure.

Objectives:

Looking for a new targetable molecule in the treatment of LPP, we sought to verify whether IL-17 expression is increased in scalp biopsies from patients with active scalp lesions of LPP.

Methods:

Horizontal sections of hematoxylin and eosin–stained slides from 40 scalp biopsies of active LPP were retrospectively collected and stained with the monoclonal antibody against IL-17 (Abcam, Cambridge, MA; ab79056, dilution 1:100). Twenty biopsies from patients with chronic telogen effluvium served as controls because of their morphological resemblance to the normal scalp. Statistical analysis was performed using IBM SPSS Statistics for Windows (IBM Corporation, Armonk, NY).

Results:

The main finding was the positive cytoplasmic expression of IL-17 in the perifollicular fibrosis of the affected follicles in LPP which was statistically significant compared with the controls (P< 0.0001). The labeled cells were identified as fibroblasts based on their spindle shape and fascicular concentric arrangement in tight perifollicular distribution. Although most of the LPP specimens (n = 35; 87.5%) also revealed cytoplasmic IL-17 expression in the lichenoid inflammatory infiltrate, the results were not statistically significant (P= 0.1351).

Conclusion:

Our immunohistochemistry results show that blocking the IL-17 inflammatory pathway may interfere with the progression of the perifollicular fibrosis and inflammation in LPP.
Monkeypox Virus Outbreak 2022: Key Epidemiologic, Clinical, Diagnostic, and Prevention Considerations
Authors: Kwong Jeffrey , McNabb Katherine C. , Voss Joachim G. , Bergman Alanna , McGee Kara , Farley Jason
Published: October 2022

Monkeypox is a zoonotic infection that manifests as dermatologic lesions that may be painful or pruritic and can appear on the face, trunk, extremities, genitals, and mucosal surfaces. In 2022, cases of monkeypox increased exponentially and it was declared a public health emergency by the World Health Organization and the U.S. Department of Health and Human Services. Unlike previous monkeypox outbreaks, the current situation has disproportionately affected men who have sex with men and seems to be associated with lower mortality. Options for treatment and prevention are limited. The distribution and availability of vaccines and antivirals has posed challenges for patients, clinicians, and public health systems. Early recognition and management of persons with monkeypox is critical in controlling the spread of this infection. This article reviews key features of monkeypox and highlights current recommendations for clinical management, prevention, and considerations for persons with HIV. Implications for public health and nursing are discussed.
Labia Minora Transplantation With Local Flap for Reconstruction of Full-Thickness Defect of the Lower Eyelid
Authors: Kasai Shogo , Katsuren Kyoko , Kuba Ryogo , Asato Reiko
Published: October 2022

Large lower eyelid full-thickness defects require reconstruction before closure. Although several methods for replantation of the posterior lamella are reported, there are advantages and disadvantages. Herein, the authors report reconstruction of the posterior lamella of the lower eyelid by labia minora transplantation. A 70-year-old woman developed basal cell carcinoma of the right lower eyelid. Excision of the tumor resulted in a full-thickness defect of 25 mm in width on the central portion of the lower eyelid. The posterior lamella was reconstructed by labia minora transplantation, whereas the anterior lamella was reconstructed using the angular flap. There were no perioperative problems, and 2 years after the operation, the esthetic appearance and function was favorable. The labia minora mucosa has almost no donor trouble functionally and has both hardness and elasticity. Although there are some disadvantages, labia minora transplantation would be useful for posterior lamella reconstruction of the lower eyelid.
Polo-like kinase and Aurora B kinase phosphorylate and cooperate with the CIF1-CIF2 complex to promote cytokinesis initiation in
Trypanosoma brucei
Authors: Kurasawa Yasuhiro , Lee Kyu Joon , Hu Huiqing , Pham Kieu T. M. , Li Ziyin
Published: October 2022

Cytokinesis in eukaryotes is regulated by a Polo-like kinase-mediated and Aurora B kinase-mediated signalling pathway that promotes the assembly of the actomyosin contractile ring, a cytokinesis machinery conserved across evolution from yeast to humans.
Trypanosoma brucei
, an early divergent parasitic protozoan, employs an actomyosin-independent mechanism for its unusual cytokinesis that is controlled by a regulatory pathway comprising the Polo-like kinase TbPLK, the Aurora B kinase TbAUK1 and multiple trypanosomatid-specific regulators. However, whether any of these trypanosomatid-specific regulators function as substrates of TbPLK and/or TbAUK1 and how they cooperate with TbPLK and TbAUK1 to promote cytokinesis remain unknown. Here, we demonstrate that TbPLK and TbAUK1 phosphorylate the cytokinesis regulators CIF1 and CIF2 on multiple sites within their intrinsically disordered regions. We further show that TbPLK localization depends on its interaction with CIF1 from S/G2 phases, that TbPLK maintains CIF1 and CIF2 localization from G2 phase until early mitosis, and that TbAUK1 maintains CIF1 and CIF2 localization from late mitosis. Finally, we demonstrate that the cytokinesis regulators CIF4 and FPRC are not substrates of TbPLK and TbAUK1, and that they function upstream of TbPLK and TbAUK1 in the cytokinesis regulatory pathway. Together, these results provide insights into the functional interplay and the order of actions between the two protein kinases and the trypanosomatid-specific cytokinesis regulators in
T. brucei
.
Internal anatomy of a fossilized embryonic stage of the Cambrian-Ordovician scalidophoranMarkuelia
Authors: Dong Xi-ping , Duan Baichuan , Liu Jianbo , Donoghue Philip C. J.
Published: October 2022

The Wangcun fossil Lagerstätte in Hunan, South China, has yielded hundreds of fossilized embryos ofMarkuelia hunanensisrepresenting different developmental stages. Internal tissues have only rarely been observed, impeding further understanding of the soft tissue anatomy, phylogenetic affinity and evolutionary significance ofMarkuelia. In this study, we used synchrotron radiation X-ray tomographic microscopy (SRXTM) to study a new collection of fossil embryos from the Wangcun fossil Lagerstätte. We describe specimens exhibiting a spectrum of preservation states, the best of which preserves palisade structures underneath the cuticle of the head and tail, distinct from patterns of centripetal mineralization of the cuticle and centrifugal mineralization of hypha-like structures, seen elsewhere in this specimen and other fossils within the same assemblage. Our computed tomographic reconstruction of these mineralization phases preserves the gross morphology of (i) longitudinal structures associated with the tail spines, which we interpret as the proximal ends of longitudinal muscles, and (ii) a ring-shaped structure internal to the introvert, which we interpret as a ring-shaped brain, as anticipated of the cycloneuralian affinity ofMarkuelia. This is the first record of a fossilized nervous system in a scalidophoran, and the first instance in Orsten-style preservation, opening the potential for further such records within this widespread mode of high-fidelity three-dimensional preservation.
Macrophage targeting of nitazoxanide-loaded transethosomal gel in cutaneous leishmaniasis
Authors: Khalid Husna , Batool Sibgha , Din Fakhar ud , Khan Salman , Khan Gul Majid
Published: October 2022

Topical delivery is preferable over systemic delivery for cutaneous leishmaniasis, because of its easy administration, reduced systemic adverse effects and low cost. Nitazoxanide (NTZ) has broad-spectrum activity against various parasites and has the potential to avoid drug resistance developed by enzymatic mutations. NTZ oral formulation is associated with severe dyspepsia and stomach pain. Herein, NTZ-transethosomes (NTZ-TES) were prepared and loaded into chitosan gel (NTZ-TEG) for topical delivery. NTZ-TES were prepared by the thin-film hydration method and optimized statistically via the Box-Behnken method. The optimized formulation indicated excellent particle size (176 nm), polydispersity index (0.093), zeta potential (−26.4 mV) and entrapment efficiency (86%). The transmission electron microscopy analysis showed spherical-sized particles and Fourier-transform infrared spectroscopy analysis indicated no interaction among the excipients. Similarly, NTZ-TEG showed optimal pH, desirable viscosity and good spreadability. NTZ-TES and NTZ-TEG showed prolonged release behaviour and higher skin penetration and deposition in the epidermal/dermal layer of skin in comparison with the NTZ-dispersion. Moreover, NTZ-TES showed higher percentage inhibition, lower half-maximal inhibitory concentration (IC
50
) against promastigotes and higher macrophage uptake. Additionally, skin irritation and histopathology studies indicated the safe and non-irritant behaviour of the NTZ-TEG. The obtained findings suggested the enhanced skin permeation and improved anti-leishmanial effect of NTZ when administered as NTZ-TEG.
Theoretical estimates of the parameters of longitudinal undular bores in polymethylmethacrylate bars based on their measured initial speeds
Authors: Hooper Curtis G. , Khusnutdinova Karima R. , Huntley Jonathan M. , Ruiz Pablo D.
Published: October 2022

We study the evolution of the longitudinal release wave that is generated by induced tensile fracture as it propagates through solid rectangular polymethylmethacrylate (PMMA) bars of different constant cross-section. High-speed multi-point photoelasticity is used to register the strain wave at three distances from the fracture site in each experiment. In all cases, oscillations develop at the bottom of the release wave that exhibit the qualitative features of an undular bore. The pre-strain, post-strain, strain rate of the release wave and the cross-section dimensions determine the evolution of the oscillations. From the wave speed and strain rate close to the fracture site, we estimate the strain rate of the release wave as well as the growth of the amplitude and duration of the leading oscillation away from the fracture site by using formulae derived from the simple analytical solution of the linearized Gardner equation (linearized near the pre-strain level at fracture). Our estimates are then compared to experimental data, where good agreements of these three parameters are found between the predictions of the model and the experimental observations. Thus, we developed an approach to estimating the key characteristics of the developing unsteady undular bore based on the measured initial speeds of the longitudinal and shear waves. This does not require a prior knowledge of the elastic moduli for the conditions of the experiments, which in PMMA are known to be strain rate dependent.
Validating hybrid fire testing with full-physical twin experiments
Authors: Neuenschwander Martin , Schulthess Patrick , Mosalam Khalid M. , Knobloch Markus
Published: October 2022

Real fire incidents show that structural systems have specific fire-induced redundancies that make them perform better than classical structural fire analysis predicts. Properly validated hybrid fire testing has the potential to tap into such redundancies for designs. In this study, we conceived and implemented a comprehensive and novel physics-based validation strategy for hybrid fire testing. We developed a laboratory-scale thermo-mechanical proof-of-concept problem that is representative for structural systems exposed to compartment fires. We solved the proof-of-concept problem using our novel thermo-mechanical hybrid solution procedure (Schulthesset al.2020Comput. Struct.238, 106301 (doi:10.1016/j.compstruc.2020.106301)) and compared the resulting hybrid model response against the results from a full-physical laboratory set-up of the same proof-of-concept problem, which we call a full-physical twin experiment. Full-physical twin experiments constitute the top layer of a suite of benchmark tests any specific hybrid fire testing procedure must pass to qualify not only as theoretically accurate and correctly functioning but also (and more importantly) as physically sound and able to yield realistic simulation results. This paper delivers such a first-of-its-kind physics-based validation, and in doing so, the first comprehensively validated method for hybrid fire testing—a method that now allows fire test facilities to conduct meaningful full-scale hybrid fire tests of entire structural systems.
Gravity, duality and conformal symmetry
Authors: Hull Chris
Published: October 2022

The

(
4
,
0
)

supermultiplet in six dimensions contains a fourth-rank tensor gauge field with the symmetries of the Riemann tensor and is superconformal, with

32
+
32

supersymmetries. Dimensional reduction on a circle gives the five dimensions

N
=
8

supergravity multiplet, with the fourth-rank tensor reducing to the graviton. If there is an interacting

(
4
,
0
)

theory, it should reduce to the full

N
=
8

supergravity theory and so would give a conformal theory of gravity that would reduce to conventional gravity with the usual two-derivative action at low energies. This paper revisits the conjecture that a non-lagrangian interacting

(
4
,
0
)

superconformal theory arises from a strong coupling limit of five-dimensional supergravity (suitably embedded in

M

-theory) describing

M

-theory at energies beyond the Planck scale. A key test for this is identified:

M

-theory toroidally compactified to five dimensions should have certain BPS states carrying a singlet central charge. These 1/2 BPS states are not related to any of the standard BPS states by dualities and do not correspond to non-singular soliton solutions—they appear to correspond to singular solutions related to gravitational instantons. Such states are needed to provide the Kaluza–Klein modes for the compactified six-dimensional theory. If there are no such states, then the conjecture is false, while the presence of such states would be strong indication that the conjecture could be true.
The dinosaurian femoral head experienced a morphogenetic shift from torsion to growth along the avian stem
Authors: Egawa Shiro , Griffin Christopher T. , Bishop Peter J. , Pintore Romain , Tsai Henry P. , Botelho João F. , Smith-Paredes Daniel , Kuratani Shigeru , Norell Mark A. , Nesbitt Sterling J. , Hutchinson John R. , Bhullar Bhart-Anjan S.
Published: October 2022

Significant evolutionary shifts in locomotor behaviour often involve comparatively subtle anatomical transitions. For dinosaurian and avian evolution, medial overhang of the proximal femur has been central to discussions. However, there is an apparent conflict with regard to the evolutionary origin of the dinosaurian femoral head, with neontological and palaeontological data suggesting seemingly incongruent hypotheses. To reconcile this, we reconstructed the evolutionary history of morphogenesis of the proximal end of the femur from early archosaurs to crown birds. Embryological comparison of living archosaurs (crocodylians and birds) suggests the acquisition of the greater overhang of the femoral head in dinosaurs results from additional growth of the proximal end in the medial-ward direction. On the other hand, the fossil record suggests that this overhang was acquired by torsion of the proximal end, which projected in a more rostral direction ancestrally. We reconcile this apparent conflict by inferring that the medial overhang of the dinosaur femoral head was initially acquired by torsion, which was then superseded by mediad growth. Details of anatomical shifts in fossil forms support this hypothesis, and their biomechanical implications are congruent with the general consensus regarding broader morpho-functional evolution on the avian stem.
Epidemiological dynamics of bacteriocin competition and antibiotic resistance
Authors: Lehtinen Sonja , Croucher Nicholas J. , Blanquart François , Fraser Christophe
Published: October 2022

Bacteriocins, toxic peptides involved in the competition between bacterial strains, are extremely diverse. Previous work on bacteriocin dynamics has highlighted the role of non-transitive ‘rock–paper–scissors’ competition in maintaining the coexistence of different bacteriocin profiles. The focus to date has primarily been on bacteriocin interactions at the within-host scale (i.e. within a single bacterial population). Yet in species such as
Streptococcus pneumoniae
, with relatively short periods of colonization and limited within-host diversity, ecological outcomes are also shaped by processes at the epidemiological (between-host) scale. Here, we first investigate bacteriocin dynamics and diversity in epidemiological models. We find that in these models, bacteriocin diversity is more readily maintained than in within-host models, and with more possible combinations of coexisting bacteriocin profiles. Indeed, maintenance of diversity in epidemiological models does not require rock–paper–scissors dynamics; it can also occur through a competition–colonization trade-off. Second, we investigate the link between bacteriocin diversity and diversity at antibiotic resistance loci. Previous work has proposed that bacterial duration of colonization modulates the fitness of antibiotic resistance. Due to their inhibitory effects, bacteriocins are a plausible candidate for playing a role in the duration of colonization episodes. We extend the epidemiological model of bacteriocin dynamics to incorporate an antibiotic resistance locus and demonstrate that bacteriocin diversity can indeed maintain the coexistence of antibiotic-sensitive and -resistant strains.