bluuebunny/crossref_metadata_2025 huggingface dataset:
Patterns of Major Frozen Section Interpretation Error: An In-Depth Analysis From a Complex Academic Surgical Pathology Practice
Authors: Dehan Lauren M , Lewis James S , Mehrad Mitra , Ely Kim A
Published: March 2023

Objectives

To establish baseline error rates due to misinterpretation and to identify scenarios in which major errors were most common and potentially preventable.

Methods

Our database was queried over a 3-year period for major discrepancies due to misinterpretation. These were stratified by histomorphologic setting, service, availability/type of prior material, and years of experience and subspecialization of the interpreting pathologist.

Results

The overall discordance rate between frozen section (FS) and final diagnoses was 2.9% (199/6,910). Seventy-two errors were due to interpretation, of which 34 (47.2%) were major. Major error rates were highest on the gastrointestinal and thoracic services. Of major discrepancies, 82.4% were rendered in subdisciplines outside those of the FS pathologist. Pathologists with fewer than 10 years’ experience made more errors than those with more experience (55.9% vs 23.5%, P = .006). Major error rates were greater for cases without previous material compared to those with a prior glass slide (47.1% vs 17.6%, P = .009). Common histomorphologic scenarios in which disagreements were made involved discriminating mesothelial cells from carcinoma (20.6%) and accurately recognizing squamous carcinoma/severe dysplasia (17.6%).

Conclusions

To improve performance and decrease future misdiagnoses, monitoring discordances should be a continuous component of surgical pathology quality assurance programs.
Latent disconnectome prediction of long-term cognitive-behavioural symptoms in stroke
Authors: Talozzi Lia , Forkel Stephanie J , Pacella Valentina , Nozais Victor , Allart Etienne , Piscicelli Céline , Pérennou Dominic , Tranel Daniel , Boes Aaron , Corbetta Maurizio , Nachev Parashkev , Thiebaut de Schotten Michel
Published: March 2023

Stroke significantly impacts the quality of life. However, the long-term cognitive evolution in stroke is poorly predictable at the individual level. There is an urgent need to better predict long-term symptoms based on acute clinical neuroimaging data. Previous works have demonstrated a strong relationship between the location of white matter disconnections and clinical symptoms. However, rendering the entire space of possible disconnection-deficit associations optimally surveyable will allow for a systematic association between brain disconnections and cognitive-behavioural measures at the individual level. Here we present the most comprehensive framework, a composite morphospace of white matter disconnections (disconnectome) to predict neuropsychological scores 1 year after stroke. Linking the latent disconnectome morphospace to neuropsychological outcomes yields biological insights that are available as the first comprehensive atlas of disconnectome-deficit relations across 86 scores—a Neuropsychological White Matter Atlas. Our novel predictive framework, the Disconnectome Symptoms Discoverer, achieved better predictivity performances than six other models, including functional disconnection, lesion topology and volume modelling. Out-of-sample prediction derived from this atlas presented a mean absolute error below 20% and allowed personalize neuropsychological predictions. Prediction on an external cohort achieved an R2 = 0.201 for semantic fluency. In addition, training and testing were replicated on two external cohorts achieving an R2 = 0.18 for visuospatial performance.

This framework is available as an interactive web application (http://disconnectomestudio.bcblab.com) to provide the foundations for a new and practical approach to modelling cognition in stroke. We hope our atlas and web application will help to reduce the burden of cognitive deficits on patients, their families and wider society while also helping to tailor future personalized treatment programmes and discover new targets for treatments. We expect our framework’s range of assessments and predictive power to increase even further through future crowdsourcing.
CDNF rescues motor neurons in models of amyotrophic lateral sclerosis by targeting endoplasmic reticulum stress
Authors: De Lorenzo Francesca , Lüningschrör Patrick , Nam Jinhan , Beckett Liam , Pilotto Federica , Galli Emilia , Lindholm Päivi , Rüdt von Collenberg Cora , Mungwa Simon Tii , Jablonka Sibylle , Kauder Julia , Thau-Habermann Nadine , Petri Susanne , Lindholm Dan , Saxena Smita , Sendtner Michael , Saarma Mart , Voutilainen Merja H
Published: March 2023

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease that affects motor neurons in the spinal cord, brainstem and motor cortex, leading to paralysis and eventually to death within 3–5 years of symptom onset. To date, no cure or effective therapy is available. The role of chronic endoplasmic reticulum stress in the pathophysiology of amyotrophic lateral sclerosis, as well as a potential drug target, has received increasing attention.

Here, we investigated the mode of action and therapeutic effect of the endoplasmic reticulum-resident protein cerebral dopamine neurotrophic factor in three preclinical models of amyotrophic lateral sclerosis, exhibiting different disease development and aetiology: (i) the conditional choline acetyltransferase-tTA/TRE-hTDP43-M337V rat model previously described; (ii) the widely used SOD1-G93A mouse model; and (iii) a novel slow-progressive TDP43-M337V mouse model. To specifically analyse the endoplasmic reticulum stress response in motor neurons, we used three main methods: (i) primary cultures of motor neurons derived from embryonic Day 13 embryos; (ii) immunohistochemical analyses of spinal cord sections with choline acetyltransferase as spinal motor neuron marker; and (iii) quantitative polymerase chain reaction analyses of lumbar motor neurons isolated via laser microdissection.

We show that intracerebroventricular administration of cerebral dopamine neurotrophic factor significantly halts the progression of the disease and improves motor behaviour in TDP43-M337V and SOD1-G93A rodent models of amyotrophic lateral sclerosis. Cerebral dopamine neurotrophic factor rescues motor neurons in vitro and in vivo from endoplasmic reticulum stress-associated cell death and its beneficial effect is independent of genetic disease aetiology. Notably, cerebral dopamine neurotrophic factor regulates the unfolded protein response initiated by transducers IRE1α, PERK and ATF6, thereby enhancing motor neuron survival.

Thus, cerebral dopamine neurotrophic factor holds great promise for the design of new rational treatments for amyotrophic lateral sclerosis.
Trajectories of systolic blood pressure decline in kidney transplant donors prior to circulatory death and delayed graft function
Authors: Lin Yingxin , Teixeira-Pinto Armando , Craig Jonathan C , Opdam Helen , Chapman Jeremy C , Pleass Henry , Carter Angus , Rogers Natasha M , Davies Christopher E , McDonald Stephen , Yang Jean , Lim Wai H , Wong Germaine
Published: March 2023

Background

Kidneys donated after circulatory death suffer a period of functional warm ischaemia before death, which may lead to early ischaemic injury. Effects of haemodynamic trajectories during the agonal phase on delayed graft function (DGF) is unknown. We aimed to predict the risk of DGF using patterns of trajectories of systolic blood pressure (SBP) declines in Maastricht category 3 kidney donors.

Methods

We conducted a cohort study of all kidney transplant recipients in Australia who received kidneys from donation after circulatory death donors, divided into a derivation cohort (transplants between 9 April 2014 and 2 January 2018 [462 donors]) and a validation cohort (transplants between 6 January 2018 and 24 December 2019 [324 donors]). Patterns of SBP decline using latent class models were evaluated against the odds of DGF using a two-stage linear mixed effects model.

Results

In the derivation cohort, 462 donors were included in the latent class analyses and 379 donors in the mixed effects model. Of the 696 eligible transplant recipients, 380 (54.6%) experienced DGF. Ten different trajectories, with distinct patterns of SBP decline were identified. Compared with recipients from donors with the slowest decline in SBP after withdrawal of cardiorespiratory support, the adjusted odds ratio (aOR) for DGF was 5.5 [95% confidence interval (CI) 1.38–28.0] for recipients from donors with a steeper decline and lowest SBP [mean 49.5 mmHg (standard deviation 12.5)] at the time of withdrawal. For every 1 mmHg/min reduction in the rate of decline of SBP, the respective aORs for DGF were 0.95 (95% CI 0.91–0.99) and 0.98 (95% CI 0.93–1.0) in the random forest and least absolute shrinkage and selection operator models. In the validation cohort, the respective aORs were 0.95 (95% CI 0.91–1.0) and 0.99 (95% CI 0.94–1.0).

Conclusion

Trajectories of SBP decline and their determinants are predictive of DGF. These results support a trajectory-based assessment of haemodynamic changes in donors after circulatory death during the agonal phase for donor suitability and post-transplant outcomes.
Heat stress reveals a fertility debt owing to postcopulatory sexual selection
Authors: Baur Julian , Zwoinska Martyna , Koppik Mareike , Snook Rhonda R , Berger David
Published: March 2023

Climates are changing rapidly, demanding equally rapid adaptation of natural populations. Whether sexual selection can aid such adaptation is under debate; while sexual selection should promote adaptation when individuals with high mating success are also best adapted to their local surroundings, the expression of sexually selected traits can incur costs. Here we asked what the demographic consequences of such costs may be once climates change to become harsher and the strength of natural selection increases. We first adopted a classic life history theory framework, incorporating a trade-off between reproduction and maintenance, and applied it to the male germline to generate formalized predictions for how an evolutionary history of strong postcopulatory sexual selection (sperm competition) may affect male fertility under acute adult heat stress. We then tested these predictions by assessing the thermal sensitivity of fertility (TSF) in replicated lineages of seed beetles maintained for 68 generations under three alternative mating regimes manipulating the opportunity for sexual and natural selection. In line with the theoretical predictions, we find that males evolving under strong sexual selection suffer from increased TSF. Interestingly, females from the regime under strong sexual selection, who experienced relaxed selection on their own reproductive effort, had high fertility in benign settings but suffered increased TSF, like their brothers. This implies that female fertility and TSF evolved through genetic correlation with reproductive traits sexually selected in males. Paternal but not maternal heat stress reduced offspring fertility with no evidence for adaptive transgenerational plasticity among heat-exposed offspring, indicating that the observed effects may compound over generations. Our results suggest that trade-offs between fertility and traits increasing success in postcopulatory sexual selection can be revealed in harsh environments. This can put polyandrous species under immediate risk during extreme heat waves expected under future climate change.
Morphological integration during postnatal ontogeny: implications for evolutionary biology
Authors: Hubbe Alex , Machado Fabio A , Melo Diogo , Garcia Guilherme , Sebastião Harley , Porto Arthur , Cheverud James , Marroig Gabriel
Published: March 2023

How covariance patterns of phenotypes change during development is fundamental for a broader understanding of evolution. There is compelling evidence that mammalian cranium covariance patterns change during ontogeny. However, it is unclear to what extent variation in covariance patterns during ontogeny can impact the response to selection. To tackle this question, we explored: (a) the extent to which covariance patterns change during postnatal ontogeny; (b) in which ontogenetic stages covariance patterns differ the most; and (c) the extent to which the phenotypic covariance pattern at different ontogenetic stages can be explained by the same processes determining additive genetic covariance. We sampled the postnatal ontogenetic series for both marsupials and placentals. Within each ontogenetic series, we compared covariance matrices (P-matrices) at different ontogenetic stages. Furthermore, we compared these P-matrices to two target matrices [adult P-matrix and an additive genetic covariance matrix (G-matrix)]. Our results show that for all ontogenetic series, covariance patterns from weaning onward are conserved and probably shaped by the same processes determining the G-matrix. We conclude that irrespective of eventual differences in how selection operates during most of the postnatal ontogeny, the net response to such pressures will probably not be affected by ontogenetic differences in the covariance pattern.
Evolutionary loss of complexity in animal signals: cause and consequence
Authors: Ord Terry J , Diesmos Arvin , Ahmad Norhayati , Das Indraneil
Published: March 2023

We identified hypotheses for the cause and consequences of the loss of complexity in animal signals and tested these using a genus of visually communicating lizards, the Southeast Asian Draco lizards. Males of some species have lost the headbob component from their display, which is otherwise central to the communication of this genus. These males instead display a large, colorful dewlap to defend territories and attract mates. This dewlap initially evolved to augment the headbob component of the display, but has become the exclusive system of communication. We tested whether the loss of headbobs was caused by relaxed selection, habitat-dependent constraints, or size-specific energetic constraints on display movement. We then examined whether the consequences of this loss have been mitigated by increased signaling effort or complexity in the color of the dewlap. It appears the increased cost of display movement resulting from the evolution of large body size might have contributed to the loss of headbobs and has been somewhat compensated for by the evolution of greater complexity in dewlap color. However, this evolutionary shift is unlikely to have maintained the complexity previously present in the communication system, resulting in an apparent detrimental loss of information potential.
Impact of hyaluronan size on localization and solubility of the extracellular matrix in the mouse brain
Authors: Egorova Diana , Nomura Yoshihiro , Miyata Shinji
Published: March 2023

Hyaluronan (HA) is a central component of the extracellular matrix (ECM) in the brain and plays a pivotal role in neural development and plasticity. Brain HA exists in 2 distinct forms of the ECM: the diffuse ECM, which is soluble in saline and detergents, and the condensed ECM, which forms aggregates, such as perineuronal nets (PNNs). Although the physiological functions of HA significantly differ depending on its size, size differences in HA have not yet been examined in the 2 ECM types, which is partly because of the lack of methods to rapidly and accurately measure the molecular weight (MW) of HA. In this study, we established a simple method to simultaneously assess the MW of HA in multiple crude biological samples. HA was purified through single-step precipitation from tissue extracts using biotinylated HA-binding protein and streptavidin-coupled magnetic beads, followed by separation on gel electrophoresis. By applying this method to HA in the mouse brain, we revealed that the condensed ECM contained higher MW HA than the diffuse ECM. Higher MW HA and lower MW HA exhibited different spatial distributions: the former was confined to PNNs, whereas the latter was widely present throughout the brain. Furthermore, the limited degradation of HA showed that only higher MW HA was required to form an insoluble HA-aggrecan complex. The present study demonstrated that the MW of HA in the brain strongly correlates with the localization and solubility of the ECM it forms.
Assessment of Jordanian community pharmacists’ confidence to provide health services and advice on self-medication for women during pregnancy and breastfeeding
Authors: Saadeh Alaa , Jaradat Roa’a , Jarab Anan S , Saadeh Noura
Published: March 2023

Objectives

The purpose of this study was to describe the services provided by community pharmacists and their confidence in providing advice on self-medication for women during pregnancy and breastfeeding.

Methods

A cross-sectional, questionnaire-based study was distributed online to community pharmacists across Jordan in the period from August through December 2020. The questionnaire identified the services most frequently offered to women throughout pregnancy or breastfeeding and evaluated the community pharmacists’ confidence in providing advice on self-medication and other services for this population group.

Key findings

A total of 340 community pharmacists completed the questionnaire. Most of them were female (89.4%), and just over half (55%) had less than 5 years of experience. The services offered by community pharmacists to women throughout pregnancy were dispensing medicine (49.1%), and dispensing herbal products (48.5%), whereas the services mainly provided for women during breastfeeding were providing advice on contraception (71.5%), and dispensing medication (45.3%).The most frequent complaints reported by women during pregnancy were gastrointestinal and urinary symptoms, and for women during lactation low milk supply and contraception. Regarding pharmacists’ confidence in providing advice on self-medication, nearly half of the respondents (50% and 49.7%) reported that they had confidence in solving medication and health challenges during pregnancy and breastfeeding, respectively.

Conclusion

Although community pharmacists provided different services for women who were pregnant or breastfeeding, many did not feel confident handling them. Continuous training programs are required to enhance community pharmacists’ ability to provide adequate care for women during pregnancy and breastfeeding.
Transcriptome investigation on the multicellular behavior ofBacillus velezensisBs916 anchoring surfactin
Authors: Dong Fei , Ren Shiying , Liu Jiachen , Bilal Muhammad , Li Bin , Chen Xin , Liu Xuehui , Zhong Haijing , Zang Shanshan , Yuan Mengxian , Luo Chuping , Jiang Jihong
Published: March 2023

Aims

To provide valuable information for a comprehensive understanding of the multicellular behavior of Bacillus velezensis Bs916 regulated by surfactin and other natural signals by Transcriptome.

Methods and results

Transcriptomics revealed a distinct effect on gene expression alterations caused by disruption of the surfactin gene cluster(Δsrf) and 100 µg/ml surfactin addition(Δsrf + SRF). A total of 1573 differential expression genes were identified among Bs916, Δsrf, and Δsrf + SRF and grouped into eight categories based on their expression profiles. RT-qPCR analysis of 30 candidate genes showed high consistency with those of transcriptome. Additionally, the expression of eight candidate genes regulated by surfactin in a dose-dependent manner was revealed by lacZ fusion. Based on the above evidence, we proposed that surfactin can act as an extracellular signal for monitoring biofilm formation in Bs916 by directly regulating the expression of AbrB, DegS-degU, and SinI-SinR, and indirectly regulating the phosphorylation of ComA and Spo0A.

Conclusions

The biofilm of Δsrf was unable to restore significantly by surfactin addition, combined inclusion of surfactin (SRF), exopolysaccharide (EPS), and γ-poly-dl-glutamic acid (γ-PGA), results in significant restoration of Δsrf biofilm formation, thereby a preliminary model was presented about the molecular mechanism by which the signaling molecule surfactin regulates Bs916 multicellular behavior.
Triple combination of SPR741, clarithromycin, and erythromycin againstAcinetobacter baumanniiand its tolerant phenotype
Authors: Li Zehao , She Pengfei , Liu Yaqian , Xu Lanlan , Li Yimin , Liu Shasha , Hussain Zubair , Li Linhui , Yang Yifan , Wu Yong
Published: March 2023

Aims

Extensively drug-resistant (XDR) Acinetobacter baumannii poses a severe threat to public health due to its ability to form biofilms and persister cells, which contributes to critical drug resistance and refractory device-associated infections. A novel strategy to alleviate such an emergency is to identify promising compounds that restore the antimicrobial susceptibility of existing antibiotics against refractory infections.

Methods and Results

Here, we found a significant synergy among three combinations of SPR741, clarithromycin and erythromycin with a potent antimicrobial activity against XDR A. baumannii (SPR741/CLA/E at 8/10/10 μg ml–1 for XDR AB1069 and at 10/16/10 μg ml–1 for XDR AB1208, respectively). Moreover, the triple combination therapy exhibits a significant antipersister and antibiofilm effect against XDR strains. Mechanistic studies demonstrate that SPR741 may promote intracellular accumulation of macrolides by permeabilizing the outer membrane as well as disrupting membrane potential and further enhance the quorum sensing inhibition activity of the macrolides against XDR A. baumannii and its biofilms. In addition, the triple combination of SPR741 with clarithromycin and erythromycin was not easy to induce resistance in A. baumannii and had effective antimicrobial activity with low toxicity in vivo.

Significance and Impact of the Study

Collectively, these results reveal the potential of SPR741 in combination with clarithromycin and erythromycin as a clinical therapy for refractory infections caused by XDR A. baumannii.
Actinobacteria as a source of biofertilizer/biocontrol agents for bio-organic agriculture
Authors: Kaari Manigundan , Manikkam Radhakrishnan , Annamalai Kishore Kumar , Joseph Jerrine
Published: March 2023

The global human population keeps growing and natural energy supplies are depleting, creating a threat to environmental demands, food security, and energy supply. As a result, increased agricultural output is required to accomplish the rising population's food demands. A strong reliance on chemical fertilizers to boost food production has harmed the environment and human health, and it is becoming too expensive as well. One of the potential solution to this problem is to use beneficial microorganisms as a substitute for artificial fertilizers in food production. Actinobacteria have been used as the most successful and long-lasting microorganisms throughout evolution. They are thought to be one of the most primordial living forms on our planet. Actinobacteria, particularly Streptomyces, have proved their ability to formulate biofertilizers in the agricultural sector by supplying nutrients to plants for better growth, increasing yield, managing abiotic and biotic stress, and resisting phytopathogen assault. This review describes the mechanism of actinobacterial biofertilizers used in the current agricultural market and their challenges and future importance to sustainable agriculture.
Fungal diversity and surfactant-producing fungi in oil contaminated environments
Authors: Chotard Mélanie , Lucchesi Marie-Elisabeth , Hamouche Lydia , Tréguer Sylvie , Lelchat Florian , Floch Stéphane Le , Mounier Jérôme
Published: March 2023

Aims

To investigate fungal diversity and biosurfactant-producing fungi in four oil-contaminated sites.

Methods and results

Water and sediment samples were collected from four sites in Brittany (France), over two periods, in winter/spring and summer. Fungal diversity was investigated using a metagenetic approach targeting the ITS2 region. Surface-active compound production of 701 fungal isolates collected from these samples after direct plating or following enrichment was assessed using oil spreading and Parafilm M tests. Fungal communities were highly diverse and the main dominant fungal taxa were members of the Cladosporium, Penicillium, Pseudeurotium, Phoma, Aspergillus, and Trichoderma as well as Ochroconis, Fusicolla, and Aureobasidium genera in specific sites. A total of 179 isolates (25.5% of total isolates) were positive to at least one of the screening tests, while 105 were positive to both tests. Major genera among the positive isolates were Fusarium, Trichoderma, Candida, and Penicillium. Six isolates belonging to Aureobasidium pullulans, Mucor griseocyanus, Trichoderma citrinoviride, Trichoderma harzianum, Trichodermalongibrachiatum, and Diaporthe eres showed promising activities.

Conclusions

The present study highlighted the fungal diversity of oil-contaminated environments and the fact that surface-active compound production is widespread in fungi originating from these habitats.
Identifying the mechanism of missingness for unspecified diabetic retinopathy disease severity in the electronic health record: an IRIS® Registry analysis
Authors: Hatfield Meghan , Nguyen Thai Hien , Chapman Richard , Myrick Alayna C , Leng Theodore , Mbagwu Michael , Baxi Shrujal , Torres Aracelis Z , Borkar Durga S
Published: March 2023

Observational studies of diabetic retinopathy (DR) using electronic health record data often determine disease severity using International Classification of Disease (ICD) codes. We investigated the mechanism of missingness for DR severity based on ICD coding using the American Academy of Ophthalmology IRIS® Registry. We included all patient encounters in the registry with a DR ICD-9 or ICD-10 code between January 1, 2014 and June 30, 2021. Demographic, clinical, and practice-level characteristics were compared between encounters with specified and unspecified disease severity. Practices were divided into quartiles based on the proportion of clinical encounters with unspecified DR severity. Encounters with unspecified disease severity were associated with significantly older patient age, better visual acuity, and lower utilization of ophthalmic procedures. Higher volume practices and retina specialist practices had lower proportions of clinical encounters with unspecified disease severity. Results strongly suggest that DR disease severity related to ICD coding is missing not at random.
An unknown collector of Late Antique textiles from Egypt
Authors: Głowa Anna
Published: March 2023

The purpose of this paper is to present an outline sketch of Carl Kallenberg, a little-known nineteenth-century collector of antiquities, and the circumstances of his purchase of Late Antique textiles from Egypt, and to summarize the further history of this ensemble. Calling on an essay published in 1890 by Kallenberg in Der Sammler and on an unpublished notebook of the antiquary and collector Robert Forrer, the paper examines the potential of these sources to complement our knowledge of the beginnings of interest in Late Antique textiles from Egypt, traces the provenance of Kallenberg’s specimens in early collections and assesses their possible whereabouts today.
Global DNA 5-hydroxymethylcytosine level and its chromosomal distribution in four rye species
Authors: Kalinka Anna , Starczak Marta , Gackowski Daniel , Stępień Edyta , Achrem Magdalena
Published: March 2023

The rye genome has a large size with a high level of cytosine methylation, which makes it particularly convenient for studying the occurrence of potential cytosine demethylation intermediates. Levels of global 5-hydroxymethylcytosine (5hmC) were analysed by enzyme-linked immunosorbent assay (ELISA) and mass spectrometry in four rye species: Secale cereale, Secale strictum, Secale sylvestre, and Secale vavilovii. The amount of 5hmC showed interspecific variation, and was also variable among organs, i.e. coleoptiles, roots, leaves, stems, and caryopses. 5-Formylcytosine (5fC), 5-carboxycytosine (5caC), and 5-hydroxymethyluracil (5hmU) were also found to be present in the DNA of all species; their global level varied among species and organs. The 5hmC level clearly correlated with the 5-methylcytosine (5mC) quantity. The mass spectrometry analysis carried out on the 5mC enriched fraction supported this relationship. Highly methylated sequences also contained higher amounts of 5fC and most of all 5hmU, but not 5caC. The analysis of the distribution of 5hmC in chromosomes distinctly indicated the co-localization of 5mC with 5hmC in the same chromosomal regions. The regularities in the levels of 5hmC and other rare modifications of bases in the DNA may indicate that they play a role in the regulation of the rye genome.
Single-nucleus RNA sequencing and mRNA hybridization indicate key bud events and LcFT1 and LcTFL1-2 mRNA transportability during floral transition in litchi
Authors: Yang Ming-Chao , Wu Zi-Chen , Chen Ri-Yao , Abbas Farhat , Hu Gui-Bing , Huang Xu-Ming , Guan Wei-Song , Xu Yi-Song , Wang Hui-Cong
Published: March 2023

In flowering plants, floral induction signals intersect at the shoot apex to modulate meristem determinacy and growth form. Here, we report a single-nucleus RNA sequence analysis of litchi apical buds at different developmental stages. A total of 41 641 nuclei expressing 21 402 genes were analyzed, revealing 35 cell clusters corresponding to 12 broad populations. We identify genes associated with floral transition and propose a model that profiles the key events associated with litchi floral meristem identity by analyzing 567 identified floral meristem cells at single cell resolution. Interestingly, single-nucleus RNA-sequencing data indicated that all putative FT and TFL1 genes were not expressed in bud nuclei, but significant expression was detected in bud samples by RT–PCR. Based on the expression patterns and gene silencing results, we highlight the critical role of LcTFL1-2 in inhibiting flowering and propose that the LcFT1/LcTFL1-2 expression ratio may determine the success of floral transition. In addition, the transport of LcFT1 and LcTFL1-2 mRNA from the leaf to the shoot apical meristem is proposed based on in situ and dot-blot hybridization results. These findings allow a more comprehensive understanding of the molecular events during the litchi floral transition, as well as the identification of new regulators.
Lessons learned during the war in Ukraine: a report from the Renal Disaster Relief Task Force of the ERA
Authors: Tuğlular Serhan , Luyckx Valerie , Vanholder Raymond , Skoberne Andrej , Wiecek Andrzej , Nistor İonut , Pawlowicz-Szlarska Ewa , Shroff Rukshana , Ivanov Dmytro , Eckardt Kai-Uwe , Noruisiene Edita , Gallego Daniel , Loboda Olena , Sever Mehmet S
Published: March 2023

People living with kidney disease are among the most vulnerable at times of natural or man-made disasters. In addition to their unpredictable course, armed conflicts impose a major threat given the disruption of infrastructure, sanitation and access to food, water and medical care. The ongoing war in Ukraine has once more demonstrated the importance of preparedness, organization, coordination and solidarity during disasters. People living with kidney disease face serious challenges given their dependence on life-sustaining treatment, irrespective of whether they remain in the war zone or are displaced internally or externally. This especially affects those requiring kidney replacement therapy, dialysis or transplantation, but also patients with other kidney diseases and the medical staff who care for them. Soon after the war started, the European Renal Association assigned a Renal Disaster Relief Task Force dedicated to support the people living with kidney disease and the nephrology community in Ukraine. This report summarizes the major challenges faced, actions taken and lessons learned by this task force. We anticipate that the experience will help to increase preparedness and mitigate the devastating effects of armed conflicts on the kidney community in the future and propose to establish an international collaboration to extend this effort to other parts of the world facing similar challenges.
Breakthrough Invasive Fungal Infection After Coadministration of Venetoclax and Voriconazole
Authors: Hall Victoria G , Tang Kenny , Kumar Deepali , Rotstein Coleman , Chow Signy , Chan Steven M , Husain Shahid , Hosseini-Moghaddam Seyed M
Published: March 2023

Venetoclax requires a 75% dose reduction when coadministered with voriconazole. In a 10-year historical cohort of treatment with venetoclax, we did not observe a worse hematologic outcome in patients who received voriconazole prophylaxis versus those who did not. Subtherapeutic voriconazole levels and a triazole exposure history may contribute to breakthrough invasive fungal infection.
Tomato sucrose transporter SlSUT4 participates in flowering regulation by modulating gibberellin biosynthesis
Authors: Liang Yufei , Bai Jiayu , Xie Zhilong , Lian Zhaoyuan , Guo Jia , Zhao Feiyang , Liang Yan , Huo Heqiang , Gong Haijun
Published: March 2023

The functions of sucrose transporters (SUTs) differ among family members. The physiological function of SUT1 has been studied intensively, while that of SUT4 in various plant species including tomato (Solanum lycopersicum) is less well-understood. In this study, we characterized the function of tomato SlSUT4 in the regulation of flowering using a combination of molecular and physiological analyses. SlSUT4 displayed transport activity for sucrose when expressed in yeast (Saccharomyces cerevisiae), and it localized at both the plasma membrane and tonoplast. SlSUT4 interacted with SlSUT1, causing partial internalization of the latter, the main phloem loader of sucrose in tomato. Silencing of SlSUT4 promoted SlSUT1 localization to the plasma membrane, contributing to increased sucrose export and thus increased sucrose level in the shoot apex, which promoted flowering. Both silencing of SlSUT4 and spraying with sucrose suppressed gibberellin biosynthesis through repression of ent-kaurene oxidase and gibberellin 20-oxidase-1 (2 genes encoding key enzymes in gibberellin biosynthesis) expression by SlMYB76, which directly bound to their promoters. Silencing of SlMYB76 promoted gibberellin biosynthesis. Our results suggest that SlSUT4 is a functional SUT in tomato; downregulation of SlSUT4 expression enhances sucrose transport to the shoot apex, which promotes flowering by inhibiting gibberellin biosynthesis.
Social-Ecological Resilience of Indigenous Adolescents in the United States and Canada
Authors: Hodgson Christine , Godfrey Timian , DeCoteau Rhea N. , Allison-Burbank Joshuaa D. , Taylor-Piliae Ruth
Published: March 2023

For the past decade, resilience research with American Indian/Alaska Native and First Nations/Métis/Inuit adolescents has improved our understanding of how adolescents overcome mental health challenges. A new situation-specific theory is presented to guide nurses in applying the evidence to their practice with Indigenous adolescents in the United States and Canada. The social-ecological resilience of indigenous adolescents (SERIA) theory was derived from integrating (a) existing social-ecological frameworks by Bronfenbrenner, Ungar, and Burnette and Figley, (b) findings from a systematic review of 78 studies about resilience factors for mental health of Indigenous adolescents, (c) clinical experience, and (d) Indigenous knowledge.
The Addition of Daytime Physiotherapeutic Scoliosis-specific Exercises to Adolescent Idiopathic Scoliosis Nighttime Bracing Reduces Curve Progression
Authors: Zapata Karina A. , McIntosh Amy L. , Jo Chan-Hee , Virostek Donald
Published: March 2023

Background:

The effectiveness of physiotherapeutic scoliosis-specific exercises (PSSE) in addition to nighttime bracing compared with nighttime bracing alone is unknown. The purpose of this prospective comparative study was to evaluate the effectiveness of PSSE in skeletally immature patients with adolescent idiopathic scoliosis treated with nighttime bracing (PSSE group) compared with the standard of care of nighttime bracing alone (control group).

Methods:

Patients with adolescent idiopathic scoliosis thoracolumbar or lumbar primary curves <35 degrees at Risser stage 0 who wore a Providence brace were prospectively enrolled into the PSSE or control group. A temperature sensor recorded the number of hours of brace wear. The PSSE group was instructed in the Schroth-based physical therapy method and a home exercise program for at least 15 minutes per day, 5 days per week, for 1 year.

Results:

Seventy-four patients (37 PSSE, 37 controls) were followed until the final visit of skeletal maturity or surgery. The PSSE and control groups had similar baseline Cobb angles (24 vs. 25 degrees) and average hours of brace wear (8.0 vs. 7.3 h). The PSSE group had no change in curve magnitude at the final visit compared with curve progression in the control group (1 vs. 7 degrees, P<0.01). Furthermore, the PSSE group had a lower rate of curve progression >5 degrees at the final visit (14% vs. 43%, P<0.01). The PSSE group also had less conversion to full-time bracing after 1 year (5% vs. 24%, P=0.046), but differences were no longer significant at the final visit (14% vs. 27%).

Conclusions:

In this prospective series of patients in nighttime Providence braces, the addition of Schroth-based physical therapy reduced curve progression after 1 year and at skeletal maturity. These findings can educate motivated families interested in PSSE.

Level of Evidence:

Level II.
Risk Factors for Venous Thromboembolic Events in Children With Acute Musculoskeletal Infections
Authors: Purtell Sarah R. , Thornhill Dianne , Loi Michele , Lockwood Justin , Kim John S. , MacBrayne Christine E. , DeVine Mackenzie N. , Sanders Julia , Searns Justin
Published: March 2023

Background and Objectives:

Venous thromboembolic events (VTE) complicate acute hematogenous musculoskeletal infections (MSKIs) among hospitalized children. However, there is limited guidance for which specific MSKI patients are at the greatest VTE risk. This study aimed to identify VTE risk factors for children hospitalized with MSKIs.

Methods:

A retrospective chart review was performed of children hospitalized with MSKIs at a single quaternary care pediatric hospital during a 9-year period. Patients with chronic MSKIs, non-hematogenous infections, or significant contributing comorbidities were excluded. Demographic and clinical characteristics were compared between patients with and without VTE using forward stepwise conditional multivariable logistic regression to identify VTE risk factors.

Results:

Among 335 included patients, 7 (2.1%) developed a VTE. There was no difference in age, sex, or obesity rates for those with or without VTE. Patients with methicillin-resistant Staphylococcus aureus (MRSA) infections and/or critical illness were more likely to develop a VTE with summative adjusted odds ratios of 31.7 and 26.4, respectively. In addition, patients with VTEs had longer hospitalizations (median 4.7 vs. 12.8 d, P<0.001), longer courses of intravenous antimicrobials (median 3.7 vs. 13.5 d, P=0.001), and longer time to fever resolution (median 25.7 vs. 162 h, P=0.004).

Conclusions:

VTE prevalence among children with acute MSKIs is low. MRSA infection and critical illness significantly increase the risk for VTE development in these patients. Future prospective studies are needed to determine if VTEs in high-risk MSKI patients can be prevented.
Intravenous-oral itraconazole versus oral posaconazole in preventing invasive fungal diseases for acute leukemia patients
Authors: Liu Li , Pei Xiaolei , Ma Runzhi , He Yi , Zhang Rongli , Wei Jialin , Ma Qiaoling , Zhai Weihua , Pang Aiming , Jiang Erlie , Han Mingzhe , Yang Donglin , Feng Sizhou
Published: March 2023

Invasive fungal diseases (IFDs) are major and lethal infectious complications for patients with neutropenia after chemotherapy. Prophylaxis with intravenous and oral suspended itraconazole (200 mg Q12h intravenously × 2 days followed by 5 mg/kg·d orally in twice) or oral suspension of posaconazole (200 mg Q8h) was administered for preventing IFDs. The only 2 episodes of proven IFDs were not included after propensity-score matching (PSM), while the incidence of possible IFDs was 8.2% (9/110) in itraconazole group and 1.8% (2/110) in posaconazole group, respectively (P = .030). In clinical failure analysis, the failure rate of posaconazole group was lower as compared to the itraconazole group (2.7% vs 10.9%, P = .016). Both intravenous-oral itraconazole and posaconazole suspension are effective in preventing IFDs, while posaconazole suspension seems more tolerable.
Antisense oligonucleotide therapy for proline-23-histidine autosomal dominant retinitis pigmentosa
Authors: Justin Grant A. , Girach Aniz , Maldonado Ramiro S.
Published: March 2023

Purpose of review

To discuss antisense oligonucleotide (ASON) therapy for autosomal dominant retinitis pigmentosa (adRP) caused by the proline-23-histidine (P23H) mutation in the rhodopsin gene.

Recent findings

Viral and nonviral therapies to treat adRP are currently under investigation. A promising therapeutic option is a nonviral approach using ASONs. This form of genetic therapy has demonstrated a dose-dependent and highly selective reduction of P23H mutant rhodopsin mRNA in animal models, and it is currently being investigated as a human phase 1/2 clinical trial.

There are promising new therapies to treat adRP. ASON has shown encouraging results in animal models and has undergone a phase 1 clinical trial. ASON does not use a viral vector, is delivered with standard intravitreal injection, and its effects are reversible.
Postoperative discoloration of a multifocal hydrophobic acrylic lens: case report with laboratory analyses
Authors: Bundogji Nour , Hawn Vivian S. , Micheletti J. Morgan , Sahler Ruth , Werner Liliana
Published: March 2023

Introduction:

A case of discoloration of a multifocal hydrophobic acrylic intraocular lens (IOL), which was explanted and exchanged as well as underwent laboratory analysis, is reported.

Patient and Clinical Findings:

The patient presented with a corrected distance visual acuity of 20/50 and glare in the right eye 8 years after implantation. Slitlamp examination revealed a nasally decentered IOL with a whitish-brownish haze throughout.

Diagnosis, Intervention, and Outcomes:

The discolored IOL (ZMB00) was explanted and exchanged for a 3-piece IOL (sulcus fixation). Grossly, the explanted IOL showed a whitish discoloration of the optic only after hydration, corresponding to a yellowish-brownish discoloration observed under light microscopy. Back light scattering revealed bulk scatter throughout the optic. Light transmittance (%T) showed a slight progressive decrease starting at 500 nm when compared with %T in the directions for use (DFUs). Although modulation transfer function analysis demonstrated similar values to the control lens, the contrast of U.S. Air Force targets appeared slightly decreased.

Conclusions:

To the authors' knowledge, this is the first reported case of a discolored ZMB00 IOL that underwent explantation and laboratory assessment. Although current analyses did not reveal the etiology of the discoloration, surgeons should be aware of this possible occurrence with this lens design and carefully assess signs and symptoms before explantation.
Leprosy-like reaction occurred during the treatment of a cutaneous Mycobacterium haemophilum infection: A case report
Authors: Chen Weiquan , Zhang Ruining , Zhou Shunting , Zhu Yao , Wu Wei , Yang Yanping , Cai Chuanchuan
Published: March 2023

Rationale:

Mycobacterium haemophilum is a rare pathogen, belongs to the slowly-growing nontuberculous mycobacterium family, and shares a close evolutionary relationship with Mycobacterium leprae. It is a fastidious organism that requires special media(iron or hemin supplementation)and conditions (incubation at 30–32°C) for growth, which differs from most other pathogenic mycobacteria.

Patient concerns:

A 43-year-old Asian male presented to our outpatient department due to the appearance of multiple infiltrative erythematous nodules and ulcerations on the extremities for more than 2 months.

Diagnoses:

Acid-fast bacteria were detected in the specimen and sequencing for hsp65 and 16S rRNA genes of the pathogen extracted from the biopsy tissue identified as M haemophilum. The diagnosis of cutaneous M haemophilum infection was established.

Interventions:

The patient received a 3-drug regimen (oral clarithromycin 1.0 g/d, rifampicin 0.6 g/d, and moxifloxacin 1.0 g/d) and local hot compression therapy, the dose of immunosuppressant was reduced.

Outcomes:

The lesions gradually improved after 6 months of continuous antibiotic therapy. There is no recurrence of erythema papules and nodules.

Lessons:

This case shows that the patient’s condition may be exacerbated immediately after the initiation of anti-nontuberculous mycobacterium therapy, which is analogous to the leprosy reaction. A high degree of clinical suspicion for the underlying disease is critical to avoid unnecessary interruption of treatment.
Intramedullary brachytherapy for the treatment of long bone metastatic disease: A case report
Authors: O'Neill David Eric , Gannavarapu Bhavani , Hrycushko Brian , Folkert Michael , Timmerman Robert , Callan Alexandra
Published: March 2023

Case:

A 56-year-old woman with metastatic melanoma and femoral lesions with impending pathologic fracture was indicated for intramedullary brachytherapy (IMBT) and intramedullary nail.

Conclusions:

IMBT + intramedullary nail is a new technique for the treatment of long bone metastases. IMBT maximizes radiation to the tumor and minimizes radiation to surrounding tissues. It allows the patient to resume systemic treatment expediently. Our cadaver model and patient were both treated for femoral metastases; however, this technique allows for the treatment of any long bone. This is a safe technique that minimizes treatment time compared with other standard radiation regimens.
Virologic response to antiretroviral therapy in people with HIV and tuberculosis in high tuberculosis burden countries
Authors: De Castro Nathalie , Chazallon Corine , Brites Carlos , Messou Eugène , Khosa Celso , Laureillard Didier , Chau Giang D. , Pilotto José H. , Eholié Serge , Delaugerre Constance , Molina Jean-Michel , Wittkop Linda , Grinsztejn Beatriz , Marcy Olivier
Published: March 2023

Objective:

We sought to compare virologic outcomes on antiretroviral therapy (ART) between people with HIV (PWH) also treated for tuberculosis in the different countries who participated to two randomized trials.

Design:

Pooled analysis of two randomized clinical trials.

Methods:

In the phase II Reflate TB and phase III Reflate TB2 trials conducted in Brazil, Côte d’Ivoire, Mozambique and Vietnam, ART-naïve PWH treated for tuberculosis were randomized to receive raltegravir or efavirenz. We assessed country differences in baseline characteristic using Wilcoxon tests and chi-square, or Fisher's exact test. We used logistic regression to analyze determinants of virologic success, defined as week-48 plasma HIV-1 RNA <50 copies/ml.

Results:

Of 550 participants (140 from Brazil, 170 from Côte d’Ivoire, 129 from Mozambique and 111 from Vietnam) with median baseline HIV-1 RNA of 5.4 log10 copies/ml, 362 (65.8%) achieved virologic success at week 48. Virologic success rates were: 105/140 (75.0%) in Brazil, 99/170 (58.2%) in Côte d’Ivoire, 84/129 (65.1%) in Mozambique and 74/111 (66.7%) in Vietnam (P = 0.0233). Baseline HIV-1 RNA, but not the country, was independently associated with virologic success: baseline HIV-1 RNA ≥500 000 copies/ml (reference), HIV RNA <100 000 copies/ml odds ratio 3.12 [95% confidence interval (CI) 1.94; 5.01] and HIV-1 RNA 100 000–499 999 copies/ml odds ratio: 1.80 (95% CI 1.19; 2.73). Overall, 177/277 (63.9%) patients treated with raltegravir and 185/273 (67.9%) patients treated with efavirenz had a plasma HIV-1 RNA <50 copies/ml at week 48.

Conclusions:

Virologic response to antiretroviral therapy in PWH with TB varied across countries but was mainly driven by levels of pretreatment HIV-1 RNA.