bluuebunny/crossref_metadata_2025 huggingface dataset:
Infectious etiologies of persistent and chronic diarrhea in Asian developing countries: A systematic review and meta‐analysis
Authors: Koh Matthew Chung Yi , Tan Shi Ni , Ngiam Jinghao Nicholas , Tambyah Paul Anantharajah , Siah Kewin Tien Ho
Published: May 2024

Infectious causes of diarrhea contribute significantly to morbidity in Asia. We conducted a systematic review and meta‐analysis of the prevalence of infectious etiologies of persistent and chronic diarrhea in Asian adults. Searches were performed on PubMed and Scopus for studies from January 1, 1970, to May 30, 2023. Sixteen studies were identified and included. The meta‐analysis was conducted with the random‐effects method, estimating the pooled prevalence of groups of infectious pathogens as causes of persistent and chronic diarrhea among Asian adults. The findings were highly heterogeneous and indicative of publication bias. The majority of studies were conducted on persons living with human immunodeficiency virus infection (PLHIV). The studies were predominantly from low‐income and middle‐income Asian countries. The most common cause was parasitic, with a pooled prevalence of 0.52 (95% confidence interval 0.28–0.65, I2 = 99%, Cochran's Q = 1027.44, P < 0.01), followed by bacterial, fungal, and viral causes, which were substantially rarer. Negative microbiological testing was also common, with a pooled prevalence for a negative test being 0.37 (95% confidence interval 0.17–0.52, I2 = 99%, Cochran's Q = 1027.44, P < 0.01). Subgroup analyses of studies conducted among PLHIV, from year 2000 and among those conducted in Southeast Asia showed a similar prevalence of parasitic causes of diarrhea. In conclusion, in Asian adults with persistent and chronic diarrhea, parasitic causes were most prevalent. However, the estimate of true prevalence is limited by significant heterogeneity among the available studies. More study in this field is required, especially examining PLHIV in the post‐antiretroviral therapy era and from high‐income countries.
Feeding practices and dietary intake in Brazilian children with Down syndrome: A cross‐sectional study
Authors: Genovesio M. C. R. S. , Monteiro L. S. , da Silva A. V. , Rodrigues P. R. M. , Baumblatt A. P. , Ribas S. A.
Published: May 2024

Background

Studies investigating the quality of the diet and dietary intake of children with Down syndrome (DS) are required because the features attributed to the syndrome can affect growth, development and quality of life.

Methods

This cross‐sectional study was conducted with 77 Brazilian children with DS between 5 and 36 months of age receiving care at the multidisciplinary outpatient clinic of the University Hospital. Participants' sociodemographic, dietary and anthropometric data were collected from the care protocols. Dietary data were collected from 24‐h recalls and dietary practices were assessed according to the WHO dietary guidelines. Associations between inadequate feeding practices and demographic variables were assessed using logistic regression models.

Results

Fruits, milk or infant formula, vegetables, beans and meat were among the five most consumed foods by the children investigated. Overall, we observed a high number of cases of early weaning (50.6%), low minimum dietary diversity (MDD; 40.3%), inadequate consistency for age (64.9%), early presence of ultra‐processed foods (76.6%), sugars and sweets (33.8%) in the diet of the children with DS. In the associations of inadequate feeding practices by age group, low MDD [odds ratio (OR): 18.6; 95% confidence interval (CI): 3.4; 57.1] and inadequate consistency (OR: 6.65; 95% CI: 1.8; 24.7) were more frequent among children aged below 12 months while this relationship was inverse for early introduction of sugar and sweets (OR: 0.04; 95% CI: 0.01; 0.29).

Conclusion

Our findings showed a high number of cases of inadequate dietary practices in children with DS investigated, which could adversely affect the long‐term health of this population.
The geography of acquisitions and greenfield investments: Firm heterogeneity and regional institutional conditions
Authors: Amendolagine Vito , Crescenzi Riccardo , Rabellotti Roberta
Published: May 2024

This paper investigates how institutional conditions at national and regional levels shape the decisions of Multinational Enterprises (MNEs) to invest abroad by means of either acquisitions or greenfield investments. The empirical analysis covers all foreign direct investment (FDI) projects in the European Union by the largest MNEs in the world to study alternative choices by the same firm and account for firm‐level characteristics in investment decisions. The empirical results show that—other things being equal—regions with stronger investment eco‐systems are more likely to attract acquisitions, while greenfield investments are more likely in regions with comparatively weaker systemic conditions. Howerver, the regional quality of institutions makes a fundamental difference to the nature of the investment projects attracted by regions: those with high quality of government can attract greenfield investments undertaken by the most productive MNEs. By improving their quality of government, local, and regional policy makers can attract higher quality greenfield investment projects to their constituencies, potentially breaking the vicious circle between low productivity areas and low productivity FDI.
Effects of vitamin K2 administration on guided bone regeneration in diabetic rats
Authors: Duman Irmak , Tanrıverdi Gamze , Öztürk Özener Hafize
Published: May 2024

Aim

The present study aimed to investigate the histomorphometric and immunohistochemical impacts of vitamin K2 on guided bone regeneration (GBR) in calvarial critical‐size defects (CSDs) in diabetic rats.

Methods

A total of 30 rats were used in this study, comprising 12 non‐diabetic (control) rats and 18 with streptozotocin‐nicotinamide‐induced experimental Diabetes mellitus (DM). In all rats, two calvarial CSDs were created: one defect was left empty (E), the other was treated with bovine‐derived bone graft and collagen‐based resorbable membrane (GM). Study groups were as follows: control rats administered saline (n = 6, C‐E and C‐GM groups) or vitamin K2 (n = 6, CK‐E and CK‐GM groups) and diabetic rats administered saline (n = 6, DM‐E and DM‐GM groups) or vitamin K2 (n = 6, DMK‐E and DMK‐GM groups). After 4 weeks of saline or vitamin K2 administration, the rats were euthanized. Bone defect healing and new bone formation were assessed histomorphometrically, and osteocalcin and osteopontin levels were examined immunohistochemically.

Results

Percentage of new bone formation was greater in CK‐GM vs. CK‐E and in DMK‐GM vs. DMK‐E [d = 3.86 (95% CI = 16.38–28.61), d = 1.86, (95% CI = 10.74–38.58), respectively, p < .05]. Bone defect healing scores were higher in CK‐GM vs. CK‐E and in DMK‐GM vs. DMK‐E [d = 2.69 (95% CI = ‐2.12 to −0.87), d = 3.28 (95% CI = 0.98–1.91), respectively, p < .05]. Osteocalcin expression levels were elevated in CK‐GM vs. CK‐E, in DMK‐GM vs. DMK‐E [d = 1.19 (95% CI = 0.08–1.41), d = 1.10 (95% CI = 0.02–1.22), respectively p < .05]. Vitamin K2 enhanced osteocalcin expression levels in DMK‐E vs. DM‐E [d = 2.78, (95% CI = 0.56–1.53), p < .05] and in DMK‐GM vs. DM‐GM [d = 2.43, (95% CI = 0.65–2.10), p < .05]. Osteopontin expression was enhanced in defects treated with GM vs. E defects [C‐GM vs. C‐E, d = 1.56 (95% CI = 0.38–2.01); CK‐GM vs. CK‐E, d = 1.91 (95% CI = 0.49–1.72); DM‐GM vs. DM‐E, d = 2.34 (95% CI = ‐1.12 to −0.50); DMK‐GM vs. DMK‐E, d = 2.00 (95% CI = 0.58–1.91), p < .05].

Conclusion

The research findings suggest that administering vitamin K2 in GBR for rats with DM favorably impacts bone healing in CSDs, presenting an adjunctive strategy for bone regeneration.
The efficacy of ball blankets on insomnia in depression in outpatient clinics: A randomised crossover multicentre trial
Authors: Kristiansen Sanne Toft , Videbech Poul , Speed Maria , Dionysopoulos Philip , Bjerrum Merete Bender , Larsen Erik Roj
Published: May 2024

Many patients with depression report insomnia symptoms that profoundly affect their health and well‐being. Non‐pharmacological treatments of insomnia may be preferable for some patients. In this randomised crossover trial, we investigated the efficacy of the Protac Ball Blanket® on insomnia among patients with depression. Included patients (n = 45) were diagnosed with unipolar depression, and with subjective insomnia and poor sleep quality (Pittsburgh Sleep Quality Index Score > 5). Each patient slept 2 weeks with a Protac Ball Blanket® and 2 weeks with a control duvet. Randomisation defined the order of the 2‐week sleep periods. Patients served as their own control in this design. The primary outcome was changes in total night‐time sleep. Secondary outcomes were sleep‐onset latency, number of awakenings, wake after sleep onset, daily use of pro necessitate sedatives and hypnotics, subjective sleep quality (Pittsburgh Sleep Quality Index), insomnia severity (Insomnia Severity Index), symptoms of depression (Hamilton Depression Rating Scale, Major Depression Inventory), symptoms of anxiety (Beck Anxiety Index), and patient‐reported outcomes concerning interpersonal sensitivity, neurasthenia, anxiety and depression (Self‐Reported Symptom State Scale). Paired two‐sided t‐tests were used to compare the means of the differences of the outcomes. Protac Ball Blanket® increased total night‐time sleep by 12.9 min (95% confidence interval: 1.21–24.63, p = 0.031). Among the secondary outcomes, Protac Ball Blanket® decreased Hamilton Depression Rating Scale by 2.78 (95% confidence interval: −5.44; −0.11, p = 0.042) and Insomnia Severity Index by 2.98 (95% confidence interval: −5.45; −0.50, p = 0.020). No changes were observed in sleep‐onset latency, number of awakenings, wake after sleep onset, Pittsburgh Sleep Quality Index, Major Depression Inventory, Beck Anxiety Index, Self‐Reported Symptom State Scale, and medication use. The results suggest that some patients may benefit from Protac Ball Blanket® as an add‐on non‐pharmacological treatment to improve sleep in depression.
Plant and soil microbial community assembly processes across urban vacant lots
Authors: Maehara Kaho , Iwachido Yuki , Katsuhara Himari , Tomitaka Mahoro , Seto Kensuke , Ushio Masayuki , Kagami Maiko , Sasaki Takehiro
Published: May 2024

Questions

Numerous studies on community assembly processes have been conducted in natural ecosystems. However, we know little about community assembly processes in human‐dominated urban ecosystems. Here, we asked: (1) how are the composition and functional diversity of native and exotic plant species shaped by local environment and landscape factors across urban vacant lots; and (2) how is microbial (bacterial and fungal) community composition influenced by the local environment, landscape factors, and plant species composition across urban vacant lots?

Location

We investigated 69 urban vacant lots in Yokohama, Japan.

Methods

By using a variation partitioning approach, we examined the relative importance of local environmental and landscape factors (including land use and spatial structure) in explaining variation in plant species composition and functional diversity of native or exotic species. We also explored the relative importance of local environmental and landscape factors, and plant species composition in explaining variation in microbial community composition.

Results

The spatial structure of vacant lots determined the species composition and functional diversity of plant communities, suggesting that plant community assembly is determined by dispersal limitation. However, the functional diversity of the exotic species varied randomly, which reduced the relative importance of the spatial structure of vacant lots. Plant species composition as well as the spatial structure of vacant lots were the important drivers of the composition of soil microbial communities, despite a higher proportion of unexplained variation in their composition. Finally, we found an essential contribution of earthmoving methods in explaining the variations in both plant and microbial community composition.

Conclusion

Plant and microbial community composition would be largely determined by dispersal limitation across urban vacant lots. Understanding urban community assembly is critical for predicting plant and microbial communities that play an essential role in regulating urban ecosystem functioning and services.
Intermediary safe harbour from copyright infringement in India—Alternative to the interpretative conundrum
Authors: Guha Sumeet , Matilal Shreya
Published: May 2024

The Information and Communication Technology (ICT) platforms that allow copyright owners to reach a large number of users and increase their economic fortune, contritely; enable the potential infringers preferring free‐riding to upload and distribute copyrighted materials. Under various theories of direct and secondary copyright infringement, the platforms now loosely called intermediaries are likely to become liable for copyright infringement. Like other jurisdictions, Indian law contains specific provisions to protect the intermediaries from such unanticipated liability. However, this intermediary liability and immunity law got muddied by inconsistent interpretations of the two operating statutes. Taking clues from the cross‐jurisdictional insights, this paper looks at the interpretative conundrum. Furthermore, the paper contends how the preferred interpretation is incompatible with the Berne Convention and Agreement on Trade‐Related Aspects of Intellectual Property Rights recommended three‐step doctrine for creating copyright exceptions. Ultimately, this paper advocates for a legislative intervention to clear the clouds of confusion in view of India's endeavour to enact a new law on ICT.
Alpha‐Gal, epitope responsible for allergy to red meat, in the Mediterranean tick Hyalomma lusitanicum
Authors: Valcárcel Ángela , Montero Andrea Briones , Rodero Marta , González‐Fernández Juan , Olmeda A. Sonia , Valcárcel Félix , Cuéllar Carmen
Published: May 2024

Alpha‐Gal/α‐Gal is an oligosaccharide produced by non‐primate mammals. Humans have developed an immune response mediated by anti‐α‐Gal antibodies that can trigger an allergic reaction and cause anaphylaxis. In recent years, cases of patients with delayed allergic reaction to mammalian meat have been reported worldwide. In Spain, these cases have been related to the species Ixodes ricinus L. (Ixodida: Ixodidae), whose distribution is located in the north of the country. In this work, the presence of α‐Gal in water‐soluble extracts from samples of salivary glands and digestive tracts of Hyalomma lusitanicum Koch (Ixodida: Ixodidae) both engorged and collected from vegetation were studied. The presence of that epitope was confirmed by the presence of reactive proteins of >250 kDa in both samples. The highest concentrations of α‐Gal were detected in salivary glands. Neither sex nor diet influenced the concentration of α‐Gal, which seems to indicate its endogenous production and its possible inoculation to the host during tick feeding.
Multiple myeloma complicated with light chain cast nephropathy with focal amyloidosis: A case report
Authors: He Yicao , Hua Zhijuan , Tan Hu , Zhao Congjuan , Liu Qiang , Jia Juan , Gao Yan
Published: May 2024

This case report describes a rare and interesting case of a patient with multiple myeloma complicated with light chain (LC) cast nephropathy and focal amyloidosis. The patient presented with acute kidney injury, anaemia and bone lesions. The diagnosis was confirmed by bone marrow biopsy, serum and urine electrophoresis and kidney biopsy. The patient was treated with isazomil, pomalidomide and dexamethasone combination chemotherapy, followed by autologous stem cell transplantation. The patient achieved clinical remission, stable renal function and improved serum lambda free LC levels. This case highlights the challenges and advances in the diagnosis and treatment of this condition.
The ecology of human flourishing embodying the changes we want to see in the world
Authors: McCormack Brendan
Published: May 2024

Flourishing is the highest good of all persons, but hard to achieve in complex societal systems. This challenge is borne out through the lens of the global nursing shortages with its focus on the supply of nurses to meet health system demands. However, nurses and midwives spend a significant part of their lives at work and so the need to pay attention to the conditions that facilitate flourishing at work is important. Drawing on ancient and contemporary philosophies, as well as critical, creative and embodied ways of knowing, enabling a flourishing practice ecosystem will be explored in this paper.
Evolutionary relationship of moso bamboo forms and a multihormone regulatory cascade involving culm shape variation
Authors: Liu Yan , Zhu Chenglei , Yue Xianghua , Lin Zeming , Li Hui , Di Xiaolin , Wang Jiangfei , Gao Zhimin
Published: May 2024

Moso bamboo (Phyllostachys edulis) known as Mao Zhu (MZ) in Chinese exhibits various forms with distinct morphological characteristics. However, the evolutionary relationship among MZ forms and the mechanisms of culm shape variation are still lacking. Here, the main differences among MZ forms were identified as culm shape variation, which were confirmed by analysing MZ forms (799 bamboo culms) and MZ (458 bamboo culms) populations. To unravel the genetic basis underlying the morphological variations, 20 MZ forms were subjected to whole‐genome resequencing. Further analysis yielded 3 230 107 high‐quality SNPs and uncovered low genetic diversity and high genotype heterozygosity associated with MZ forms' formation. By integrating the SNP data of 427 MZ individuals representing 15 geographic regions, the origins of eight MZ forms were successfully traced using the phylogenetic tree and the identified common heterozygous loci. Meanwhile, transcriptomic analysis was performed using shoots from MZ and its two forms with culm shape variation. The results, combined with genomic analyses, demonstrated that hormone signalling related genes played crucial roles in culm variation. Co‐expression network analysis uncovered genes associated with multiple plant hormone signal transduction, especially auxin and cytokinin were involved in culm shape variation. Furthermore, the regulatory relationships of a specific transcription factor and their target genes associated with auxin and ethylene signalling were validated by yeast one‐hybrid, electrophoretic mobility shift assays, and dual‐luciferase reporter. Overall, this study provides important insights into the culm shape variation formation in bamboo, which facilitates to breed new varieties with novel culms.
Sex‐specific phosphorus acquisition strategies and cycling in dioecious Populus euphratica forests along a natural water availability gradient
Authors: Liu Miao , Ye Liyun , Chen Liangliang , Korpelainen Helena , Niinemets Ülo , Li Chunyang
Published: May 2024

Soil phosphorus (P) availability affects plant growth and distribution. However, it is still unknown how sex‐specific variation in functional traits affects plants’ P acquisition and soil P transformation. On wet sites, female poplars had a greater specific root length (SRL), and a higher diversity of arbuscular mycorrhizal fungi (AMF) and phosphate‐solubilizing bacteria (PSB). Male poplars living on wet sites increased the abundance of AMF and PSB communities and enhanced moderately labile and highly resistant organic P mineralisation via increased phosphatase activity. In contrast, on the dry site, the abundance and diversity of AMF and PSB communities increased in females, enhancing moderately labile and highly resistant organic P mineralisation via elevating phosphatase activities. Males maintained greater SRL and promoted Ca‐P mobilisation via the release of root carboxylic acids and rhizosphere acidification on the dry site. The AMF community diversity followed a similar pattern as that of the PSB community when altering the P availability of different‐sex plants. Our results indicated that organic P and Ca‐P are the major sources of plant‐available P in natural P. euphratica forests. Seasonal shifts and geographic locations affected the share of organic and inorganic P pools, and AMF and PSB diversities, ultimately altering sex‐specific P acquisition strategies of plants.
3D LiDAR SLAM: A survey
Authors: Zhang Yongjun , Shi Pengcheng , Li Jiayuan
Published: May 2024

Simultaneous localization and mapping (SLAM) is a very challenging yet fundamental problem in the field of robotics and photogrammetry, and it is also a prerequisite for intelligent perception of unmanned systems. In recent years, 3D LiDAR SLAM technology has made remarkable progress. However, to the best of our knowledge, almost all existing surveys focus on visual SLAM methods. To bridge the gap, this paper provides a comprehensive review that summarizes the scientific connotation, key difficulties, research status, and future trends of 3D LiDAR SLAM, aiming to give readers a better understanding of LiDAR SLAM technology, thereby inspiring future research. Specifically, it summarizes the contents and characteristics of the main steps of LiDAR SLAM, introduces the key difficulties it faces, and gives the relationship with existing reviews; it provides an overview of current research hotspots, including LiDAR‐only methods and multi‐sensor fusion methods, and gives milestone algorithms and open‐source tools in each category; it summarizes common datasets, evaluation metrics and representative commercial SLAM solutions, and provides the evaluation results of mainstream methods on public datasets; it looks forward to the development trend of LiDAR SLAM, and considers the preliminary ideas of multi‐modal SLAM, event SLAM, and quantum SLAM.
How sociology can help us save ourselves
Authors: Fisher Dana R.
Published: May 2024

This article is derived from my 2024 ESS presidential address. I discuss my new book and how a sociological lens helps us to understand the process through which we can save ourselves from the climate crisis. After explaining why the state and the market have struggled to implement sufficient policies to address the climate crisis, I present the AnthroShift as a theory that explains how social actors reorient after risk pivots to open windows of opportunity for social change. I discuss why civil society is most likely to mobilize after there is a generalized sense of climate risk and summarize how climate activists are currently engaging in non‐violent civil disobedience as a first step in an expanded civil society sector that is likely to put pressure on the state and the market to help us save ourselves. I conclude by presenting three steps that can be taken to help us save ourselves from the climate crisis.
Masking and meaning during the COVID‐19 pandemic
Authors: Rieger Shannon
Published: May 2024

This article contributes to the developing sociology of COVID‐19 literature by examining situational variation in mask‐wearing behavior during the early pandemic. Using interview data collected from residents of Brooklyn, New York during 2020, I analyze how people talk about encounters with masking in various social contexts. I find that the act of wearing a mask during the early pandemic acquired multiple, contradictory meanings that compelled opposite stances toward masking. On one hand, public health campaigns helped encourage mask‐wearing by infusing masking with notions of solidarity and collective responsibility. But on the other hand, masks also obtained meanings related to distrust and emotional distance that became highly relevant in intimate social situations: masking around friends and other close social network members could be understood as symbolically destructive to the relationship. By illustrating how people collectively negotiated these countervailing meanings during interaction, the findings contribute to knowledge about how relational characteristics and interaction dynamics shaped the ways that people understood and enacted masking during the early COVID‐19 pandemic.
Roles of negative emotions and personality traits in psoriasis vulgaris: A mendelian randomization study
Authors: Zhang Min , Hu Yu , Chen Lihao , Chen Hongying , Huang Dan , Luan Chao , Zhang Jiaan , Chen Kun
Published: May 2024

Background

Many studies have indicated that negative emotions and personality traits are related to psoriasis, though few have provided causal evidence.

Methods

Our analysis utilized 15 genome‐wide association study datasets to identify instrumental variables associated with negative emotions, personality traits and psoriasis vulgaris. Two‐sample Mendelian randomization was conducted to identify the causal associations of negative emotions and personality traits with psoriasis vulgaris. To mitigate bias from multiple tests, we adjusted p‐values using the Benjamini–Hochberg method.

Results

Our study revealed causal links between negative emotions and psoriasis vulgaris, including depressed affect, worry too long, feeling hurt, guilty feelings, mood swings, unenthusiasm, miserableness, fed‐up feelings. However, there was no significant evidence of a causal relationship between feeling lonely and psoriasis vulgaris. Additionally, personality traits including neuroticism and openness to experience were found to have causal effects on psoriasis vulgaris. However, no significant evidence supported a causal relationship between agreeableness, conscientiousness, and extraversion with psoriasis vulgaris.

Conclusion

Our findings suggest that experiencing negative emotions including depressed affect, worrying excessively, feeling hurt, guilty feelings, mood swings, lack of enthusiasm, miserableness and fed‐up feelings may pose risks for psoriasis vulgaris. Additionally, neuroticism is associated with a risk of psoriasis vulgaris. Conversely, the openness trait may serve a protective role against psoriasis vulgaris.
Evaluating the efficacy and safety of letermovir compared to valganciclovir for the prevention of human cytomegalovirus disease in adult lung transplant recipients
Authors: Martinez Sydni , Sindu Devika , Nailor Michael D. , Cherrier Lauren , Tokman Sofya , Walia Rajat , Goodlet Kellie J.
Published: May 2024

Background

Lung transplant recipients are at high risk for severe cytomegalovirus (CMV) disease. Off‐label use of letermovir (LET) may avert myelotoxicity associated with valganciclovir (VGCV), but data in lung transplantation are limited. This study aims to evaluate the outcomes of LET prophylaxis among lung transplant recipients.

Methods

This retrospective, matched cohort study included lung transplant recipients who received LET for primary CMV prophylaxis following VGCV intolerance. Patients were matched 1:1 to historical VGCV controls based on age, serostatus group, and time from transplant. The primary outcome was CMV breakthrough within 1 year post‐LET initiation; secondary outcomes included hematologic changes.

Results

A total of 124 lung transplant recipients were included per group (32% CMV mismatch, D+R‐), with LET initiated a median of 9.6 months post‐transplantation. One CMV breakthrough event (0.8%) was observed in the LET group versus four (3.2%) in the VGCV group (p = .370). The median (interquartile range) white blood cell (WBC) count was 3.1 (2.1–5.6) at LET initiation which increased to 5.1 (3.9–7.2) at the end of follow‐up (p <.001). For VGCV controls, WBC was 4.8 (3.4–7.2) at baseline and 5.4 (3.6–7.2) at the end of follow‐up; this difference was not statistically significant (p = .395). Additionally, 98.4% of LET patients experienced ≥1 leukopenia episode in the year prior to LET compared to 71.8% the year after initiation (p <.001). Similar results were observed for neutropenia (48.4% and 17.7%, p <.001).

Conclusion

LET prophylaxis was associated with a low rate of CMV reactivation and leukopenia recovery. LET may represent a reasonable prophylaxis option for lung transplant recipients unable to tolerate VGCV.

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Outcomes of 15 dogs and two cats with metabone fractures treated with fluoroscopically guided normograde metabone pinning
Authors: von Pfeil Dirsko J. F. , Tan Desmond , Adams Robert , Glassman Mathieu
Published: May 2024

Objective

To report the outcomes of 15 dogs and two cats with metabone fractures treated with fluoroscopically guided normograde metabone pinning (FGNMP).

Study design

Retrospective case series.

Animals

A total of 15 client owned dogs and two cats with 57 metabone fractures.

Methods

Description of FGNMP and reporting of the following data: signalment, pre‐ and postoperative radiographs, intramedullary pin diameter used, anesthesia, surgery and coaptation times, duration to normal weightbearing and bone union, postoperative care and complications.

Results

Median surgery time was 54 min (range: 26–99), median duration of coaptation was 14 days (range: 1–5 weeks), median time to normal weightbearing was 16 days (range: 2–45) and median time to bone union was 6 weeks (range: 4–12). All cases had at least 12 months of post‐surgical follow‐up with a median follow‐up of 18 months (range: 12–70). No major complications occurred. Mild radiographic changes associated with subchondral bone sclerosis were noted on follow‐up radiographs in 13/57 fractures. All cases returned to normal gait and full (15) or acceptable (2) function.

Conclusion

In this study, FGNMP was an effective and safe technique for metabone fracture repair, requiring only short‐term external coaptation in most patients. Time to bone union and return to normal function compared favorably to previously reported techniques.

Clinical relevance

Fluoroscopically guided normograde metabone pinning provides an alternative technique for treatment of metabone fractures.
Inhibition of endocytic uptake of severe acute respiratory syndrome coronavirus 2 and endo-lysosomal acidification by diphenoxylate
Authors: Shin Jin Soo , Jang Yejin , Kim Dong-Su , Jung Eunhye , Lee Myoung Kyu , Kim Byungil , Ahn Sunjoo , Shin Yeonju , Jang Su San , Yun Chang Soo , Yoo Jongman , Lim Young Chang , Han Soo Bong , Kim Meehyein
Published: May 2024

Cell culture-based screening of a chemical library identified diphenoxylate as an antiviral agent against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The observed 50% effective concentrations ranged between 1.4 and 4.9 µM against the original wild-type strain and its variants. Time-of-addition experiments indicated that diphenoxylate is an entry blocker targeting a host factor involved in viral infection. Fluorescence microscopic analysis visualized that diphenoxylate prevented SARS-CoV-2 particles from penetrating the cell membrane and also impaired endo-lysosomal acidification. Diphenoxylate exhibited a synergistic inhibitory effect on SARS-CoV-2 infection in human lung epithelial Calu-3 cells when combined with a transmembrane serine protease 2 (TMPRSS2) inhibitor, nafamostat. This synergy suggested that efficient antiviral activity is achieved by blocking both TMPRSS2-mediated early and endosome-mediated late SARS-CoV-2 entry pathways. The antiviral efficacy of diphenoxylate against SARS-CoV-2 was reproducible in a human tonsil organoids system. In a transgenic mouse model expressing the obligate SARS-CoV-2 receptor, human angiotensin-converting enzyme 2, intranasal administration of diphenoxylate (10 mg/kg/day) significantly reduced the viral RNA copy number in the lungs by 70% on day 3. This study underscores that diphenoxylate represents a promising core scaffold, warranting further exploration for chemical modifications aimed at developing a new class of clinically effective antiviral drugs against SARS-CoV-2.
Host immunity involvement in the outcome of phage therapy against hypervirulent
Klebsiella pneumoniae
infections
Authors: Tang Miran , Yao Zhuocheng , Liu Yan , Ma Zhexiao , Zhao Deyi , Mao Zhenzhi , Wang Yue , Chen Lijiang , Zhou Tieli
Published: May 2024

Highly encapsulated hypervirulent
Klebsiella pneumoniae
(hvKp) causes severe infections. Bacteriophage therapy, an antibiotic alternative, effectively treats bacterial infections. Phage φFK1979 encoding polysaccharide depolymerases can target and disarm the capsule of hvKp FK1979, showing promise against FK1979 infection. Resistant strains induced by φFK1979 are possibly eliminated by host immunity and new phage phiR3 targeting them. We constructed varied immunocompromised FK1979 infection mouse models to assess the therapy efficacy of φFK1979 alone or in combination with phiR3. Survival rates, bacterial loads, histopathology, inflammation, and immune cell distribution of mice were studied. Prompt and adequate administration of φFK1979, rather than phiR3, significantly improved survival rates in mice with different immune statuses. However, immunocompromised mice showed lower efficacy due to reduced tolerance to low-virulence φFK1979-resistant bacteria compared to immunocompetent mice. Adding phiR3 sequentially greatly enhanced therapy efficacy for them, leading to increased survival rates and notable improvements in pathology and inflammation. Immunocompetent mice exhibited the most favorable response to φFK1979 monotherapy, as their immune system cleared φFK1979-resistant bacteria while avoiding a robust response to phiR3 combating φFK1979-resistant bacteria. This study revealed host immunity involvement in the outcome of phage therapy against infections and introduced, for the first time, personalized phage therapy strategies for hvKp-infected mice with varying immune statuses.

IMPORTANCE

Hypervirulent
Klebsiella pneumoniae
(hvKp), with high capsular polysaccharide production, can cause severe invasive infections. Capsule-targeting phage poses the potential to fight against hvKp. We previously elucidated that the capsule-targeting phage induces resistance in hvKp, while phage-resistant strains exhibit sensitivity to host innate immunity and new phages targeting them. This indicated that phage-resistant strains can be eliminated by the immune system in immunocompetent patients, whereas they may require treatment with phages targeting resistant bacteria in immunocompromised patients. HvKp can infect individuals with varying immune statuses, including both immunocompetent and immunocompromised/deficient patients. This study, for the first time, developed personalized phage therapy strategies for hvKp-infected mice with different immune statuses, optimizing phage therapy against hvKp infections. This research is expected to provide a theoretical foundation and novel insights for clinical phage therapy against hvKp infections, offering significant societal benefits and clinical value.
Discovery of novel treponemes associated with pododermatitis in elk (
Cervus canadensis
)
Authors: Deb Sushanta , Wild Margaret A. , LeClair Thomas , Shah Devendra H.
Published: May 2024

Pododermatitis, also known as treponeme-associated hoof disease (TAHD), presents a significant challenge to elk (
Cervus canadensis
) populations in the northwestern USA, with
Treponema
spp. consistently implicated in the lesion development. However, identifying species-specific
Treponema
strains from these lesions is hindered by its culture recalcitrance and limited genomic information. This study utilized shotgun sequencing,
in silico
genome reconstruction, and comparative genomics as a culture-independent approach to identify metagenome-assembled
Treponema
genomes (MATGs) from skin scraping samples collected from captive elk experimentally challenged with TAHD. The genomic analysis revealed 10 new MATGs, with 6 representing novel genomospecies associated with pododermatitis in elk and 4 corresponding to previously identified species
—Treponema pedis
and
Treponema phagedenis
. Importantly, genomic signatures of novel genomospecies identified in this study were consistently detected in biopsy samples of free-ranging elk diagnosed with TAHD, indicating a potential etiologic association. Comparative metabolic profiling of the MATGs against other
Treponema
genomes showed a distinct metabolic profile, suggesting potential host adaptation or geographic uniqueness of these newly identified genomospecies. The discovery of novel
Treponema
genomospecies enhances our understanding of the pathogenesis of pododermatitis and lays the foundation for the development of improved molecular surveillance tools to monitor and manage the disease in free-ranging elk.

IMPORTANCE

Treponema
spp. play an important role in the development of pododermatitis in free-ranging elk; however, the species-specific detection of
Treponema
from pododermatitis lesions is challenging due to culture recalcitrance and limited genomic information. The study utilized shotgun sequencing and
in silico
genome reconstruction to identify novel
Treponema
genomospecies from elk with pododermatitis. The discovery of the novel
Treponema
species opens new avenues to develop molecular diagnostic and epidemiologic tools for the surveillance of pododermatitis in elk. These findings significantly enhance our understanding of the genomic landscape of the
Treponemataceae
consortium while offering valuable insights into the etiology and pathogenesis of emerging pododermatitis in elk populations.
Loss of YhcB results in overactive fatty acid biosynthesis
Authors: Stanley Hannah M. , Trent M. Stephen
Published: May 2024

Loss of the
Escherichia coli
inner membrane protein YhcB results in pleomorphic cell morphology and clear growth defects. Prior work suggested that YhcB was directly involved in cell division or peptidoglycan assembly. We found that loss of YhcB is detrimental in genetic backgrounds in which lipopolysaccharide (LPS) or glycerophospholipid (GPL) synthesis is altered. The growth defect of Δ
yhcB
could be rescued through inactivation of the Mla pathway, a system responsible for the retrograde transport of GPLs that are mislocalized to the outer leaflet of the outer membrane. Interestingly, this rescue was dependent upon the outer membrane phospholipase PldA that cleaves GPLs at the bacterial surface. Since the freed fatty acids resulting from PldA activity serve as a signal to the cell to increase LPS synthesis, this result suggested that outer membrane lipids are imbalanced in Δ
yhcB
. Mutations that arose in Δ
yhcB
populations during two independent suppressor screens were in genes encoding subunits of the acetyl coenzyme A carboxylase complex, which initiates fatty acid biosynthesis (FAB). These mutations fully restored cell morphology and reduced GPL levels, which were increased compared to wild-type bacteria. Growth of Δ
yhcB
with the FAB-targeting antibiotic cerulenin also increased cellular fitness. Furthermore, genetic manipulation of FAB and lipid biosynthesis showed that decreasing FAB rescued Δ
yhcB
filamentation, whereas increasing LPS alone could not. Altogether, these results suggest that YhcB may play a pivotal role in regulating FAB and, in turn, impact cell envelope assembly and cell division.

IMPORTANCE

Synthesis of the Gram-negative cell envelope is a dynamic and complex process that entails careful coordination of many biosynthetic pathways. The inner and outer membranes are composed of molecules that are energy intensive to synthesize, and, accordingly, these synthetic pathways are under tight regulation. The robust nature of the Gram-negative outer membrane renders it naturally impermeable to many antibiotics and therefore a target of interest for antimicrobial design. Our data indicate that when the inner membrane protein YhcB is absent in
Escherichia coli
, the pathway for generating fatty acid substrates needed for all membrane lipid synthesis is dysregulated which leads to increased membrane material. These findings suggest a potentially novel regulatory mechanism for controlling the rate of fatty acid biosynthesis.
Genome reduction and horizontal gene transfer in the evolution of Endomicrobia—rise and fall of an intracellular symbiosis with termite gut flagellates
Authors: Mies Undine S. , Hervé Vincent , Kropp Tom , Platt Katja , Sillam-Dussès David , Šobotník Jan , Brune Andreas
Published: May 2024

Bacterial endosymbionts of eukaryotic hosts typically experience massive genome reduction, but the underlying evolutionary processes are often obscured by the lack of free-living relatives. Endomicrobia, a family-level lineage of host-associated bacteria in the phylum
Elusimicrobiota
that comprises both free-living representatives and endosymbionts of termite gut flagellates, are an excellent model to study evolution of intracellular symbionts. We reconstructed 67 metagenome-assembled genomes (MAGs) of
Endomicrobiaceae
among more than 1,700 MAGs from the gut microbiota of a wide range of termites. Phylogenomic analysis confirmed a sister position of representatives from termites and ruminants, and allowed to propose eight new genera in the radiation of
Endomicrobiaceae
. Comparative genome analysis documented progressive genome erosion in the new genus
Endomicrobiellum
, which comprises all flagellate endosymbionts characterized to date. Massive gene losses were accompanied by the acquisition of new functions by horizontal gene transfer, which led to a shift from a glucose-based energy metabolism to one based on sugar phosphates. The breakdown of glycolysis and many anabolic pathways for amino acids and cofactors in several subgroups was compensated by the independent acquisition of new uptake systems, including an ATP/ADP antiporter, from other gut microbiota. The putative donors are mostly flagellate endosymbionts from other bacterial phyla, including several, hitherto unknown lineages of uncultured
Alphaproteobacteria
, documenting the importance of horizontal gene transfer in the convergent evolution of these intracellular symbioses. The loss of almost all biosynthetic capacities in some lineages of
Endomicrobiellum
suggests that their originally mutualistic relationship with flagellates is on its decline.

IMPORTANCE

Unicellular eukaryotes are frequently colonized by bacterial and archaeal symbionts. A prominent example are the cellulolytic gut flagellates of termites, which harbor diverse but host-specific bacterial symbionts that occur exclusively in termite guts. One of these lineages, the so-called Endomicrobia, comprises both free-living and endosymbiotic representatives, which offers the unique opportunity to study the evolutionary processes underpinning the transition from a free-living to an intracellular lifestyle. Our results revealed a progressive gene loss in energy metabolism and biosynthetic pathways, compensated by the acquisition of new functions via horizontal gene transfer from other gut bacteria, and suggest the eventual breakdown of an initially mutualistic symbiosis. Evidence for convergent evolution of unrelated endosymbionts reflects adaptations to the intracellular environment of termite gut flagellates.
Key aspects of papillomavirus infection influence the host cervicovaginal microbiome in a preclinical murine papillomavirus (MmuPV1) infection model
Authors: Spurgeon Megan E. , Townsend Elizabeth C. , Blaine-Sauer Simon , McGregor Stephanie M. , Horswill Mark , den Boon Johan A. , Ahlquist Paul , Kalan Lindsay , Lambert Paul F.
Published: May 2024

Human papillomaviruses (HPVs) are the most common sexually transmitted infection in the United States and are a major etiological agent of cancers in the anogenital tract and oral cavity. Growing evidence suggests changes in the host microbiome are associated with the natural history and ultimate outcome of HPV infection. We sought to define changes in the host cervicovaginal microbiome during papillomavirus infection, persistence, and pathogenesis using the murine papillomavirus (MmuPV1) cervicovaginal infection model. Cervicovaginal lavages were performed over a time course of MmuPV1 infection in immunocompetent female
FVB/N
mice and extracted DNA was analyzed by qPCR to track MmuPV1 viral copy number. 16S ribosomal RNA (rRNA) gene sequencing was used to determine the composition and diversity of microbial communities throughout this time course. We also sought to determine whether specific microbial communities exist across the spectrum of MmuPV1-induced neoplastic disease. We, therefore, performed laser-capture microdissection to isolate regions of disease representing all stages of neoplastic disease progression (normal, low- and high-grade dysplasia, and cancer) from female reproductive tract tissue sections from MmuPV1-infected mice and performed 16S rRNA sequencing. Consistent with other studies, we found that the natural murine cervicovaginal microbiome is highly variable across different experiments. Despite these differences in initial microbiome composition between experiments, we observed that MmuPV1 persistence, viral load, and severity of disease influenced the composition of the cervicovaginal microbiome. These studies demonstrate that papillomavirus infection can alter the cervicovaginal microbiome.

IMPORTANCE

Human papillomaviruses (HPVs) are the most common sexually transmitted infection in the United States. A subset of HPVs that infect the anogenital tract (cervix, vagina, anus) and oral cavity cause at least 5% of cancers worldwide. Recent evidence indicates that the community of microbial organisms present in the human cervix and vagina, known as the cervicovaginal microbiome, plays a role in HPV-induced cervical cancer. However, the mechanisms underlying this interplay are not well-defined. In this study, we infected the female reproductive tract of mice with a murine papillomavirus (MmuPV1) and found that key aspects of papillomavirus infection and disease influence the host cervicovaginal microbiome. This is the first study to define changes in the host microbiome associated with MmuPV1 infection in a preclinical animal model of HPV-induced cervical cancer. These results pave the way for using MmuPV1 infection models to further investigate the interactions between papillomaviruses and the host microbiome.
Anomalous Josephson Effect in a Planar Hybrid Structure with the Spin–Orbit Coupling
Authors: Samokhvalov A. V.
Published: May 2024

The way of formation of controlled phase inhomogeneity in a hybrid structure consisting of a short Josephson junction between two superconducting thin films, with one electrode partially coated with a ferromagnetic insulator, has been theoretically studied. The joint action of spin splitting and the Rashba spin–orbit coupling at the superconductor–ferromagnet interface leads to the generation of a spontaneous supercurrent, which changes the transport properties of the junction. The critical current and the current–phase relation of this hybrid structure have been calculated; it has been shown that this structure can be used to form an anomalous φ0 Josephson junction with the phase shift φ0 smoothly varying over a wide range.
Direct Observation of Pinning of Abrikosov Vortices in a Specially Inhomogenious Crystal EuRbFe4As4
Authors: Sidelnikov M. S. , Palnichenko A. V. , Pervakov K. S. , Vlasenko V. A. , Zverkova I. I. , Uspenskaya L. S. , Pudalov V. M. , Vinnikov L. Ya.
Published: May 2024

In the two-phase crystal EuRbFe4As4/EuFe2As2 (1144/122), a linear ordering of Abrikosov vortices, uncharacteristic for superconducting pnictides, has been found using the method of decorating with magnetic nanoparticles. The observed chains of vortices directed along crystallographic 〈110〉 axes of the orthorhombic EuFe2As2 phase are explained by pinning of vortices in the superconducting phase 1144 on linear defects associated with the twin boundaries of the non-superconducting 122 phase.