bluuebunny/crossref_metadata_2025 huggingface dataset:
Low-intensity ultrasound ameliorates brain organoid integration and rescues microcephaly deficits
Authors: Li Xiao-Hong , Guo Di , Chen Li-Qun , Chang Zhe-Han , Shi Jian-Xin , Hu Nan , Chen Chong , Zhang Xiao-Wang , Bao Shuang-Qing , Chen Meng-Meng , Ming Dong
Published: May 2024

Human brain organoids represent a remarkable platform for modelling neurological disorders and a promising brain repair approach. However, the effects of physical stimulation on their development and integration remain unclear.

Here, we report that low-intensity ultrasound significantly increases neural progenitor cell proliferation and neuronal maturation in cortical organoids. Histological assays and single-cell gene expression analyses revealed that low-intensity ultrasound improves the neural development in cortical organoids. Following organoid grafts transplantation into the injured somatosensory cortices of adult mice, longitudinal electrophysiological recordings and histological assays revealed that ultrasound-treated organoid grafts undergo advanced maturation. They also exhibit enhanced pain-related gamma-band activity and more disseminated projections into the host brain than the untreated groups. Finally, low-intensity ultrasound ameliorates neuropathological deficits in a microcephaly brain organoid model.

Hence, low-intensity ultrasound stimulation advances the development and integration of brain organoids, providing a strategy for treating neurodevelopmental disorders and repairing cortical damage.
Secondary oral squamous cell carcinoma following haematopoietic stem cell transplantation
Authors: Zaki Faaris , Shephard Martina , Danby Robert , Pawson Rachel , Peniket Andy , Sheppard Katharine , Matin Rubeta N
Published: May 2024

We report the cases of 10 patients with oral squamous cell carcinoma (SCC) post-haematopoietic stem cell transplant (HSCT). Median latency from HSCT to oral SCC diagnosis was 10 years (range: 4–17 years), with 90% (9/10) reporting a history of chronic graft-versus-host disease (cGVHD) and 40% (4/10) exhibiting active severe manifestations of oral GvHD. Clinical findings at diagnosis included induration, ulceration, tenderness, bleeding, hyperkeratosis, speckling and lymphadenopathy. The tongue and buccal mucosa were the most common sites affected. The disease stage at presentation ranged from T1N0M0 to T4N2M0. Management included surgical resection in 90% (9/10) of patients with or without chemotherapy and/or radiotherapy. The median follow-up for the cohort was 1 year, with a 50% (5/10) mortality rate. SCC-specific mortality was 30% (3/10). Our data highlight the importance of regular, active oral and cutaneous surveillance of patients post-HSCT in specialized dermatology clinics, irrespective of GvHD severity and length of iatrogenic immunosuppression.
Epithelioid sarcoma: a rare cause of refractory chronic skin ulcers
Authors: Zhang Long , Huang Xianqiong , Cheng Qionghui , Lei Xia , Wu Jinjin , Chen Jinyi
Published: May 2024

We report two cases of chronic skin ulcers that were misdiagnosed as skin and soft tissue infections and as an inflammatory myofibroblastic tumour before the final diagnosis of epithelioid sarcoma at our institution. Our coverage of this rare but fatal tumour that can cause chronic skin ulcers is critical because early diagnosis and treatment can reduce morbidity and mortality.
An evaluation of ChatGPT compared with dermatological surgeons’ choices of reconstruction for surgical defects after Mohs surgery
Authors: Cuellar-Barboza Adrian , Brussolo-Marroquín Elizabeth , Cordero-Martinez Fanny C , Aguilar-Calderon Patrizia E , Vazquez-Martinez Osvaldo , Ocampo-Candiani Jorge
Published: May 2024

Background

ChatGPT is an open-access chatbot developed using artificial intelligence (AI) that generates human-like responses.

Objective

To evaluate the ChatGPT-4’s concordance with three dermatological surgeons on reconstructions for dermatological surgical defects.

Methods

The cases of 70 patients with nonmelanoma skin cancer treated with surgery were obtained from clinical records for analysis. A list of 30 reconstruction options was designed by the main authors that included primary closure, secondary skin closure, skin flaps and skin grafts. Three dermatological surgeons who were blinded to the real reconstruction, along with ChatGPT-4, were asked to select two reconstruction options from the list.

Results

Seventy responses were analysed using Cohen’s kappa, looking for concordance between each dermatologist and ChatGPT. The level of agreement among dermatological surgeons was higher compared with that between dermatological surgeons and ChatGPT, highlighting differences in decision making. In the selection of the best reconstruction technique, the results indicated a fair level of agreement among the dermatologists, ranging between κ 0.268 and 0.331. However, the concordance between ChatGPT-4 and the dermatologists was slight, with κ values ranging from 0.107 to 0.121. In the analysis of the second-choice options, the dermatologists showed only slight agreement. In contrast, the level of concordance between ChatGPT-4 and the dermatologists was below chance.

Conclusions

As anticipated, this study reveals variability in medical decisions between dermatological surgeons and ChatGPT. Although these tools offer exciting possibilities for the future, it is vital to acknowledge the risk of inadvertently relying on noncertified AI for medical advice.
Psychosocial comorbidities in patients with paediatric alopecia areata: a literature review
Authors: Sejdiu Zane , Hess Samantha , Jafferany Mohammad
Published: May 2024

Alopecia areata (AA), a chronic autoimmune disorder causing nonscarring hair loss, has a greater prevalence in the paediatric population. Like many visible dermatological disorders, AA can cause significant psychosocial impairment, particularly in children who are undergoing critical periods of psychosocial development. This paper investigates the psychosocial impact of AA on children. A systematic review was conducted using the PRISMA guidelines. The SCOPUS and PubMed databases were utilized with the terms ‘alopecia areata’, ‘pediatric’ and ‘psychosocial comorbidities’. Twelve articles were reviewed, with six meeting the inclusion criteria for detailed analysis. The review revealed prominent associations between AA and psychosocial comorbidities in children. Psychiatric conditions including anxiety, depression and obsessive–compulsive disorder were prevalent in paediatric patients with AA, with exacerbation due to increased disease severity. These negatively impacted the quality of life of the affected children. Additionally, the comorbidities extended beyond psychiatric diagnoses, impacting self-esteem, academic performance, peer relationships and body image satisfaction in children. This literature review highlights the significant impact of various psychosocial comorbidities in children with AA, emphasizing the need for early identification and intervention. Healthcare professionals, including psychiatrists, therapists and dermatologists, can play a significant role in treating paediatric patients with AA. Dermatologists can play a critical role in diagnosing AA, identifying psychosocial comorbidities that may arise, and referring patients to appropriate care. Future research should focus on elucidating effective screening tools for dermatologists to identify these comorbidities early, ultimately improving the overall wellbeing of children with AA.
A case of Olmsted syndrome with dramatic response to erlotinib
Authors: Oldham Jaimie , O’Toole Edel
Published: May 2024

A 63-year-old man with Olmsted syndrome, which was causing him severe pain and had been impairing his quality of life since birth, was treated with erlotinib 100 mg once daily. This led to a dramatic improvement in both his pain and quality of life. Owing to side-effects, the dose was reduced to 100 mg three times a week, which has maintained efficacy. Side-effects are now minimal.
Effectiveness of Double-Dose Dolutegravir in People Receiving Rifampin-based Tuberculosis Treatment: An Observational, Cohort Study of People With HIV From 6 Countries
Authors: Shah N Sarita , Kityo Cissy , Hughes Michael D , McCarthy Caitlyn , Wallis Carole L , Hosseinipour Mina C , Langat Deborah , Nyirenda Mulinda , Rassool Mohammed , Dawson Rodney , Joseph Yvetot , Some Fatma , Mngqibisa Rosie , Mukwekwerere Pamela Grace , Woolley Elizabeth , Godfrey Catherine , Manabe Yukari C , Mellors John W , Flexner Charles , Maartens Gary ,   ACTG A5381/Hakim Study Team, Jezile Vuyokazi S , Mwelase Thando , Louis Marie Jude Jean , François Daphie Jean , Siika Abraham , Kirui Viola , Madlala Penelope , Casey Petronella , Samaneka Wadzanai , Musodza Yeukai , Magengo Nadia , Moonsamy Suri
Published: May 2024

Background

Tenofovir-lamivudine-dolutegravir (TLD) is the preferred first-line antiretroviral therapy (ART) regimen. An additional 50-mg dose of dolutegravir (TLD+50) is required with rifampin-containing tuberculosis (TB) co-treatment. There are limited data on the effectiveness of TLD+50 in individuals with TB/human immunodeficiency virus (HIV).

Methods

We performed a prospective, observational cohort study at 12 sites in Haiti, Kenya, Malawi, South Africa, Uganda, and Zimbabwe. Participants starting TLD and rifampin-containing TB treatment were eligible. The primary outcome was HIV-1 RNA ≤1000 copies/mL at end of TB treatment.

Results

We enrolled 91 participants with TB/HIV: 75 (82%) ART-naive participants starting TLD after a median 15 days on TB treatment, 10 (11%) ART-naive participants starting TLD and TB treatment, 5 (5%) starting TB treatment after a median 3.3 years on TLD, and 1 (1%) starting TB treatment and TLD after changing from efavirenz-lamivudine-tenofovir. Median age was 37 years, 35% were female, the median CD4 count was 120 cells/mm3 (interquartile range, 50–295), and 87% had HIV-1 RNA >1000 copies/mL. Among 89 surviving participants, 80 were followed to TB treatment completion, including 7 who had no HIV-1 RNA result due to missed visits. The primary virologic outcome was assessed in 73 participants, 69 of whom (95%; 95% confidence interval, 89%–100%) had HIV-1 RNA ≤1000 copies/mL. No dolutegravir resistance mutations were detected among 4 participants with HIV-1 RNA >1000 copies/mL.

Conclusions

In programmatic settings, concurrent rifampin-containing TB treatment and TLD+50 was feasible, well tolerated, and achieved high viral suppression rates in a cohort of predominantly ART-naive people with TB/HIV.
Spectrum of Treg and self-reactive T cells: single cell perspectives from old friend HTLV-1
Authors: Ono Masahiro , Satou Yorifumi
Published: May 2024

Despite extensive regulatory T cell (Treg) research, fundamental questions on in vivo dynamics remain to be answered. The current study aims to dissect several interwoven concepts in Treg biology, highlighting the ‘self-reactivity’ of Treg and their counterparts, namely naturally-arising memory-phenotype T-cells, as a key mechanism to be exploited by a human retroviral infection. We propose the novel key concept, Periodic T cell receptor (TCR)-signalled T-cells, capturing self-reactivity in a quantifiable manner using the Nr4a3-Timer-of-cell-kinetics-and-activity (Tocky) technology. Periodic and brief TCR signals in self-reactive T-cells contrast with acute TCR signals during inflammation. Thus, we propose a new two-axis model for T-cell activation by the two types of TCR signals or antigen recognition, elucidating how Foxp3 expression and acute TCR signals actively regulate Periodic TCR-signalled T-cells. Next, we highlight an underappreciated branch of immunological research on Human T-cell Leukemia Virus type 1 (HTLV-1) that precedes Treg studies, illuminating the missing link between the viral infection, CD25, and Foxp3. Based on evidence by single-cell analysis, we show how the viral infection exploits the regulatory mechanisms for T-cell activation and suggests a potential role of periodic TCR signalling in infection and malignant transformation. In conclusion, the new perspectives and models in this study provide a working framework for investigating Treg within the self-reactive T-cell spectrum, expected to advance understanding of HTLV-1 infection, cancer, and immunotherapy strategies for these conditions.
Management of Colorectal Neoplasia in IBD Patients: Current Practice and Future Perspectives
Authors: Derks Monica E W , te Groen Maarten , van Lierop Lisa M A , Murthy Sanjay , Rubin David T , Bessissow Talat , Nagtegaal Iris D , Bemelman Willem A , Derikx Lauranne A A P , Hoentjen Frank
Published: May 2024

Inflammatory bowel disease [IBD] patients are at increased risk of developing colorectal neoplasia [CRN]. In this review, we aim to provide an up-to-date overview and future perspectives on CRN management in IBD. Advances in endoscopic surveillance and resection techniques have resulted in a shift towards endoscopic management of neoplastic lesions in place of surgery. Endoscopic treatment is recommended for all CRN if complete resection is feasible. Standard [cold snare] polypectomy, endoscopic mucosal resection and endoscopic submucosal dissection should be performed depending on lesion complexity [size, delineation, morphology, surface architecture, submucosal fibrosis/invasion] to maximise the likelihood of complete resection. If complete resection is not feasible, surgical treatment options should be discussed by a multidisciplinary team. Whereas [sub]total and proctocolectomy play an important role in management of endoscopically unresectable CRN, partial colectomy may be considered in a subgroup of patients in endoscopic remission with limited disease extent without other CRN risk factors. High synchronous and metachronous CRN rates warrant careful mucosal visualisation with shortened intervals for at least 5 years after treatment of CRN.
Insertion–Deletion Events Are Depleted in Protein Regions with Predicted Secondary Structure
Authors: Yang Yi , Braga Matthew V , Dean Matthew D
Published: May 2024

A fundamental goal in evolutionary biology and population genetics is to understand how selection shapes the fate of new mutations. Here, we test the null hypothesis that insertion–deletion (indel) events in protein-coding regions occur randomly with respect to secondary structures. We identified indels across 11,444 sequence alignments in mouse, rat, human, chimp, and dog genomes and then quantified their overlap with four different types of secondary structure—alpha helices, beta strands, protein bends, and protein turns—predicted by deep-learning methods of AlphaFold2. Indels overlapped secondary structures 54% as much as expected and were especially underrepresented over beta strands, which tend to form internal, stable regions of proteins. In contrast, indels were enriched by 155% over regions without any predicted secondary structures. These skews were stronger in the rodent lineages compared to the primate lineages, consistent with population genetic theory predicting that natural selection will be more efficient in species with larger effective population sizes. Nonsynonymous substitutions were also less common in regions of protein secondary structure, although not as strongly reduced as in indels. In a complementary analysis of thousands of human genomes, we showed that indels overlapping secondary structure segregated at significantly lower frequency than indels outside of secondary structure. Taken together, our study shows that indels are selected against if they overlap secondary structure, presumably because they disrupt the tertiary structure and function of a protein.
Funding of evidence included within public comments submitted to inform Medicare national coverage determinations
Authors: Lu Angela , Ji Robin Z , Magee Marley P D , Ross Joseph S , Ramachandran Reshma , Redberg Rita F , Dhruva Sanket S
Published: May 2024

The Centers for Medicare & Medicaid Services (CMS) relies on public comments submitted in response to proposed national coverage determinations to assist the agency in determining the coverage of items and services for Medicare beneficiaries. In a cross-sectional study, we characterized the cited evidence and what funding supported the cited evidence submitted in public comments to CMS for all therapeutic medical device national coverage determinations finalized between June 2019 and June 2022. Of 681 public comments, 159 (23%) cited at least 1 identifiable published scientific journal article. Within these 159 public comments, 198 unique articles were cited, 170 (86%) of which included funding statements or author disclosures. Among these, 96 (56%) disclosed funding from manufacturers that would benefit from Medicare coverage and/or were written by author(s) who received funding from these manufacturers. In summary, most public commenters for national coverage determinations did not cite published scientific journal articles to support their positions. Among those who did, more than half of articles were directly funded by manufacturers that would benefit from coverage. Greater funding of independent, non–industry-supported research may help provide unbiased evaluations of benefits and harms to support Medicare coverage decisions.
Heated tobacco product marketing: a mixed-methods study examining exposure and perceptions among US and Israeli adults
Authors: Cui Yuxian , Bar-Zeev Yael , Levine Hagai , LoParco Cassidy R , Duan Zongshuan , Wang Yan , Abroms Lorien C , Khayat Amal , Berg Carla J
Published: May 2024

The marketing of heated tobacco products (HTPs), like IQOS, influences consumers’ perceptions. This mixed-methods study analyzed (i) survey data (2021) of 2222 US and Israeli adults comparing perceptions of 7 IQOS attributes (design, technology, colors, customization, flavors, cost and maintenance) and 10 marketing messages (e.g. ‘Go smoke-free…’) across tobacco use subgroups and (ii) qualitative interviews (n = 84) regarding IQOS perceptions. In initial bivariate analyses, those never using HTPs (86.2%) reported the least overall appeal; those currently using HTPs (7.7%) reported the greatest appeal. Notably, almost all (94.8%) currently using HTPs also currently used cigarettes (82.0%) and/or e-cigarettes (64.0%). Thus, multivariable linear regression accounted for current cigarette/e-cigarette use subgroup and HTP use separately; compared to neither cigarette/e-cigarette use (62.8%), cigarette/no e-cigarette use (17.1%) and e-cigarette/no cigarette use (6.5%), those with dual use (13.5%) indicated greater overall IQOS appeal (per composite index score); current HTP use was not associated. Qualitative data indicated varied perceptions regarding advantages (e.g. harm, addiction and complexity) of IQOS versus cigarettes and e-cigarettes, and perceived target markets included young people, those looking for cigarette alternatives and females. Given the perceived target markets and particular appeal to dual cigarette/e-cigarette use groups, IQOS marketing and population impact warrant ongoing monitoring to inform regulation.
Participation in global value chains and M&A flows
Authors: Ciani Andrea , Gregori Wildmer Daniel
Published: May 2024

This study investigates whether companies operating in industrial sectors characterized by a higher participation in global value chains (GVC) are more likely to be involved in cross-border mergers and acquisitions (M&A). We focus on firms acquired in the EU27 during the period 2008–2020 implementing a gravity model. Results show that cross-border investments are indeed associated with sectoral GVC participation, in particular the dependence on intermediates supplied by other countries (i.e., backward GVC participation) of the target country-sector, which is positively correlated with M&A flows. This evidence is confirmed when the acquired firm operates in high-tech sectors, and when the investor is based in OECD countries. In addition, we find that companies from non-OECD countries supplying inputs to other countries (i.e., higher forward GVC participation) are more likely to pursue a cross-border acquisition.
Institutional investors and dividend payments: evidence in the oil industry
Authors: Machado João Victor , Sarti Fernando , Silveira Rodrigo Lanna Franco da
Published: May 2024

The debate over the impacts of shareholder value orientation on corporate management has been more intense with the increasing participation of institutional investors in companies’ ownership structures. In this context, the purpose of this study is to evaluate the influence of institutional investors’ shareholding on the payment of dividends in the oil industry. A regression model was used, estimated with the Generalized Method of Moments. The results indicated that the distribution of dividends is related to the profitability and the leverage of the companies, in addition to the history of distribution to shareholders. In general, the presence of institutional investors did not influence the dividend distribution. However, we observed a large participation of these investors in the ownership structure of companies in the oil and gas sector—the average control of these agents was around 25% in the companies of the sample. This study contributes to the literature regarding the influence of institutional investors on the corporate decisions of nonfinancial companies, being original in the context of the oil industry.
New Combinatorial Identity for the Set of Partitions and Limit Theorems in Finite Free Probability Theory
Authors: Arizmendi Octavio , Fujie Katsunori , Ueda Yuki
Published: May 2024

We provide a refined combinatorial identity for the set of partitions of $\{1,\dots , n\}$, which plays an important role in investigating several limit theorems related to finite free convolutions. Firstly, we present the finite free analogue of Sakuma and Yoshida’s limit theorem. That is, we provide the limit of $\{D_{1/m}((p_{d}^{\boxtimes _{d}m})^{\boxplus _{d}m})\}_{m\in{\mathbb{N}}}$ as $m\rightarrow \infty $ in two cases: (i) $m/d\rightarrow t$ for some $t>0$ or (ii) $m/d\rightarrow 0$. The second application presents a central limit theorem for finite free multiplicative convolution. We establish a connection between this theorem and the multiplicative free semicircular distributions through combinatorial identities. Our last result gives alternative proofs for Kabluchko’s limit theorems concerning the unitary Hermite and the Laguerre polynomials.
Integral Models of Moduli Spaces of Shtukas with Deep Bruhat-Tits Level Structures
Authors: Bieker Patrick
Published: May 2024

We construct integral models for moduli spaces of shtukas with deeper Bruhat-Tits level structures. We embed the moduli space of global shtukas for a deeper Bruhat-Tits group scheme into the limit of the moduli spaces of shtukas for all associated parahoric group schemes. Its schematic image defines an integral model of the moduli space of shtukas with deeper Bruhat-Tits level with favourable properties. They admit proper, surjective and generically étale level maps as well as a natural Newton stratification. In the Drinfeld case, this general construction of integral models recovers the moduli space of Drinfeld shtukas with Drinfeld level structures.
Humoral responses are enhanced by facilitating B cell viability by Fcrl5 overexpression in B cells
Authors: Ono Chisato , Kochi Yuta , Baba Yoshihiro , Tanaka Shinya
Published: May 2024

B cell initial activity is regulated through a balance of activation and suppression mediated by regulatory molecules expressed in B cells; however, the molecular mechanisms underlying this process remain incompletely understood. In this study, we investigated the function of the Fc receptor-like (Fcrl) family molecule Fcrl5, which is constitutively expressed in naive B cells, in humoral immune responses. Our study demonstrated that B cell-specific overexpression of Fcrl5 enhanced antibody (Ab) production in both T cell-independent type 1 (TI1) and T cell-dependent (TD) responses. Additionally, it promoted effector B cell formation under competitive conditions in TD responses. Mechanistically, in vitro ligation of Fcrl5 by agonistic Abs reduced cell death and enhanced proliferation in lipopolysaccharide-stimulated B cells. In the presence of anti-CD40 Abs and IL-5, the Fcrl5 ligation not only suppressed cell death but also enhanced differentiation into plasma cells. These findings reveal a novel role of Fcrl5 in promoting humoral immune responses by enhancing B cell viability and plasma cell differentiation.
Eliciting the barriers and enablers towards anaesthetists giving penicillin-based antibiotic prophylaxis to low-risk patients who have had their penicillin allergy label removed as part of a preoperative delabelling process
Authors: Roberts Neil , Fontaine Libby , Sandoe Jonathan , Tonkin-Crine Sarah , Powell Neil
Published: May 2024

Background

Some penicillin allergy labels can be removed by non-allergy specialists by direct oral challenge, but there is reluctance amongst anaesthetists to give penicillin to these patients. We aimed to assess anaesthetist beliefs about giving penicillin to patients delabelled by direct oral challenge.

Methods

A survey, developed using the Theoretical Domains Framework, was circulated to anaesthetists within a regional research network in England. Domains were rated using 5-point Likert scales. Overall and group medians were used to dichotomize domains rated by group into ‘relatively important/unimportant’ and ‘relative enabler/barrier’.

Results

We received 257 responses from six hospitals (response rate 49.7%). Seven domains were rated as important for all stakeholder groups and hospitals: Knowledge, Skills, Belief in Capabilities, Belief in Consequences, Memory/Attention/Decisions, Environmental Context and Resources, and Emotions. Social and Professional Role was also important to all respondents except those in one hospital. Intentions and Optimism were rated as important for some groups/hospitals and unimportant for others. All four other domains were rated as unimportant for all groups/hospitals. All domains rated as important were enablers for all groups/hospitals, with the exception of Memory/Attention/Decisions and Emotions, which were rated as discordant barriers/enablers between groups. This means they were acting as a barrier for some staff groups/hospitals and an enabler for others. Barrier domains (Reinforcement, Goals, Social Influences, Behavioural Regulation) were all rated unimportant.

Conclusions

Behavioural influences on giving penicillin prophylaxis to a delabelled patient are complex and nuanced. These findings could inform targeted interventions, both across and within hospitals and staff groups.
Emergence of an IncX3 plasmid co-harbouring the carbapenemase genes blaNDM-5 and blaOXA-181
Authors: Zuo Hui , Sugawara Yo , Kondo Kohei , Kayama Shizuo , Kawakami Sayoko , Uechi Kohei , Nakano Ami , Yahara Koji , Sugai Motoyuki
Published: May 2024

Background

The spread of transmissible plasmids with carbapenemase genes has contributed to a global increase in carbapenemase-producing Enterobacterales over the past two decades, with blaNDM and blaOXA among the most prevalent carbapenemase genes.

Objectives

To characterize an Escherichia coli isolate co-carrying blaNDM-5 and blaOXA-181 (JBEHAAB-19-0176) that was isolated in the Japan Antimicrobial Resistant Bacterial Surveillance in 2019–20, and to evaluate the functional advantage of carrying both genes as opposed to only one.

Methods

The whole-genome sequence of the isolate was determined using long- and short-read sequencing. Growth assay and co-culture experiments were performed for phenotypic characterization in the presence of different β-lactam antibiotics.

Results

WGS analysis showed that blaNDM-5 and blaOXA-181 were carried by the same IncX3 plasmid, pJBEHAAB-19-0176_NDM-OXA. Genetic characterization of the plasmid suggested that the plasmid emerged through the formation of a co-integrate and resolution of two typical IncX3 plasmids harbouring blaNDM-5 and blaOXA-181, which involved two recombination events at the IS3000 and IS26 sequences. When cultured in the presence of piperacillin or cefpodoxime, the growth rate of the transformant co-harbouring blaNDM-5 and blaOXA-181 was significantly higher than the transformant with only blaNDM-5. Furthermore, in co-culture where the two blaNDM-5-harbouring transformants were allowed to compete directly, the strain additionally harbouring blaOXA-181 showed a marked growth advantage.

Conclusions

The additional carriage of blaOXA-181 confers a selective advantage to bacteria in the presence of piperacillin and cefpodoxime. These findings may explain the current epidemiology of carbapenemase-producing Enterobacterales, in which bacteria carrying both blaNDM-5 and blaOXA-48-like genes have emerged independently worldwide.
The lack of EphB3 receptor prevents bone loss in mouse models of osteoporosis
Authors: Rodríguez-Sosa Mariano R , del Castillo Luis M , Belarra Adrián , Zapata Agustín G , Alfaro David
Published: May 2024

Bone homeostasis is a complex process in which some Eph kinase receptors and their ephrin ligands appear to be involved. In the present study, we address this issue by examining, both in vitro and in vivo, the role of EphB2 and EphB3 in mesenchymal stromal/stem cell (MSC) differentiation into bone tissue. This was first evaluated by quantitative reverse transcription PCR (RT-qPCR) and histological staining in MSCs cultured in specific mediums revealing that although EphB2−/− MSCs mainly expressed pro-adipogenic transcription factors, EphB3−/− MSCs showed abundant osteogenic transcripts, such as Runx2, Msx2, and Sp7. To clarify the underlying molecular mechanisms, we found that the lack of EphB3 signaling alters the genetic profile of differentiating MSCs, reducing the expression of many inhibitory molecules and antagonists of the BMP signaling pathway, and increasing Bmp7 expression, a robust bone inductor. Then, to confirm the osteogenic role of EphB3 in vivo, we studied the condition of 2 mouse models of induced bone loss (ovariectomy or long-term glucocorticoid treatment). Interestingly, in both models, both WT and EphB2−/− mice equally developed the disease but EphB3−/− mice did not exhibit the typical bone loss, nor an increase in urine Ca2+ or blood serum CTX-1. This phenotype in EphB3-KO mice could be due to their significantly higher proportions of osteoprogenitor cells and preosteoblasts, and their lower number of osteoclasts, as compared with WT and EphB2-KO mice. Thus, we conclude that EphB3 acts as a negative regulator of the osteogenic differentiation, and its absence prevents bone loss in mice subjected to ovariectomy or dexamethasone treatment.
Coevolution of non-homologous end joining efficiency and encephalization
Authors: Udroiu Ion , Sgura Antonella
Published: May 2024

Double-strand breaks (DSB), the most difficult to repair DNA damage, are mainly repaired by non-homologous end-joining (NHEJ) or homologous recombination (HR). Previous studies seem to indicate that primates, and particularly humans, have a better NHEJ system. A distinctive feature of the primate lineage (beside longevity) is encephalization, i.e., the expansion of the brain relative to body mass (BM). Using existing transcriptome data from 34 mammalian species, we investigated the possible correlations between the expression of genes involved in NHEJ and encephalization, BM, and longevity. The same was done also for genes involved in the HR pathway. We found that, while HR gene expression is better correlated with longevity, NHEJ gene expression is strongly (and better) correlated with encephalization. Since the brain is composed of postmitotic cells, DSB repair should be mainly performed by NHEJ in this organ. Therefore, we interpret the correlation we found as an indication that NHEJ efficiency coevolved with encephalization.
Sperm competition favours intermediate sperm size in a hermaphrodite
Authors: Santhosh Santhosh , Ebert Dieter , Janicke Tim
Published: May 2024

Sperm competition is a potent mechanism of postcopulatory sexual selection that has been found to shape reproductive morphologies and behaviours in promiscuous animals. Especially sperm size has been argued to evolve in response to sperm competition through its effect on sperm longevity, sperm motility, the ability to displace competing sperm, and ultimately fertilization success. Additionally, sperm size has been observed to co-evolve with female reproductive morphology. Theoretical work predicts that sperm competition may select for longer sperm but may also favour shorter sperm if sperm size trades-off with number. In this study, we studied the relationship between sperm size and postmating success in the free-living flatworm, Macrostomum lignano. Specifically, we used inbred isolines of M. lignano that varied in sperm size to investigate how sperm size translated into the ability of worms to transfer and deposit sperm in a mating partner. Our results revealed a hump-shaped relationship with individuals producing sperm of intermediate size having the highest sperm competitiveness. This finding broadens our understanding of the evolution of sperm morphology by providing empirical support for stabilizing selection on sperm size under sperm competition.
Evaluation of the most popular annual flowers sold in the United States and Europe indicates low visitation rates by pollinators and large variation among cultivars
Authors: Smitley David , Oneil Colin , Hotchkiss Erica , Runkle Erik , Studyvin Jared
Published: May 2024

To better understand how frequently pollinators visit the most popular annuals and the variation among cultivars, we evaluated 3–6 cultivars, each of petunia, impatiens, begonia, geranium, pansy, and New Guinea impatiens. These 6 annuals account for 46.6% of all garden center annual flower sales in the United States. Flower visits by honey bees, bumble bees, syrphids, other Diptera and other Hymenoptera, combined, varied 3 to 10-fold among cultivars within each of the 6 popular annuals. Begonia and impatiens were visited more frequently by pollinators than pansy, petunia, NG impatiens, and geranium. The 4 most visited cultivars, begonia ‘Cocktail Brandy’, begonia ‘Ambassador Rose Blush’, impatiens ‘Accent Coral’, and impatiens ‘Super Elfin XP White’ attracted as many pollinators as a benchmark annual, marigold ‘Alumia Vanilla Cream’, considered as moderately attractive to pollinators. Some conclusions from this research may be helpful for homeowners, landscapers, growers, and breeders. First, the most popular annual flowers are not a good choice for the purpose of attracting and supporting pollinators. However, the large variation among cultivars provides an opportunity to select cultivars that are more attractive to pollinators, particularly for begonia and impatiens. If the most pollinator-visited cultivars of begonia and impatiens are labeled and promoted as such, it would be beneficial to pollinators in urban and suburban landscapes in the USA and Europe, where they comprise 10%–20% of all annual flowers purchased from garden centers.
The Effect of Ophthalmic Antibiotics on Clinical Outcomes and Transmissibility of Conjunctivitis Associated with Haemophilus influenzae versus Other Pathogens: Secondary Analysis of a Randomized Controlled Trial
Authors: Thomas Elizabeth T , Perera-Salazar Rafael , Frost Holly M
Published: May 2024

Transmission rates among children with conjunctivitis were low and antibiotic use was not associated with reduced transmission. Policies recommending exclusion from daycare and school for conjunctivitis should be scrutinized as they may not reduce transmission and may increase unnecessary antibiotic use.
Risk prediction strategies using intraoperative physiological data in adults undergoing surgery: a systematic review study protocol
Authors: Yong Shun Qi , Ang Gauri , Stubbs Daniel J
Published: May 2024

Postoperative mortality accounts for 7.7% of all global deaths, while postoperative complications increase 1-year mortality by 60%. Risk prediction models for postoperative complications and mortality can facilitate tailored risk mitigation strategies. However, most models incorporate only preoperative patient-related factors as predictors and do not capture dynamic risks or intraoperative events. This systematic review seeks to evaluate the predictive capability of intraoperative physiology derived from routine anaesthetic monitoring and the feature extraction methods for these variables. This review will include both prospective and retrospective studies that incorporate intraoperative physiological measurements into the development, validation or updating of a statistical prediction model, to identify those at risk of major end-organ (cardiovascular, pulmonary, renal and neurological) complications and mortality up-to 90 days postoperatively. We will identify models developed in two settings: those undergoing cardiac surgery and heterogeneous adult patient cohorts undergoing non-cardiac surgery. The review will be reported according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This review will evaluate the available literature on intraoperative physiology as predictor variables, to improve feature extraction methods for risk prediction models development while understanding how to capitalize on the vast routinely collected intraoperative physiological data sets that are increasingly available. This review is registered on PROSPERO, registration number CRD42023474384.
Emerging into the world: regulation and control of dormancy and sprouting in geophytes
Authors: Kumari Nirupma , Kumari Manhas Sonali , Jose-Santhi Joel , Kalia Diksha , Sheikh Firdous Rasool , Singh Rajesh Kumar
Published: May 2024

Geophytic plants synchronize growth and quiescence with the external environment to survive and thrive under changing seasons. Together with seasonal growth adaptation, dormancy and sprouting are critical factors determining crop yield and market supply, as various geophytes also serve as major food, floriculture, and ornamental crops. Dormancy in such crops determines crop availability in the market, as most of them are consumed during the dormant stage. On the other hand, uniform/maximal sprouting is crucial for maximum yield. Thus, dormancy and sprouting regulation have great economic importance. Dormancy–sprouting cycles in geophytes are regulated by genetic, exogenous (environmental), and endogenous (genetic, metabolic, hormonal, etc.) factors. Comparatively, the temperature is more dominant in regulating dormancy and sprouting in geophytes, unlike above-ground tissues, where both photoperiod and temperature control are involved. Despite huge economic importance, studies concerning the regulation of dormancy and sprouting are scarce in the majority of geophytes. To date, only a few molecular factors involved in the process have been suggested. Recently, omics studies on molecular and metabolic factors involved in dormancy and growth regulation of underground vegetative tissues have provided more insight into the mechanism. Here, we discuss current knowledge of the environmental and molecular regulation and control of dormancy and sprouting in geophytes, and discuss challenges/questions that need to be addressed in the future for crop improvement.
The Feasibility and Efficacy of Warrior Health and Fitness: A 3-Month Fitness and Nutrition Program for Veterans
Authors: Horwitz Sarah D , Millstein Rachel A , McCarthy Megan D , Vanderweit Ryan , Fernandez Jaime , Hernandez Armando R , Wilson Victoria , Maggiolo Nicolette , Collins Emily , Hirschberg Ron , Cefalo Philip , Sylvia Louisa G
Published: May 2024

Introduction

Veterans are at risk for mental and physical health problems but may not seek traditional health care services. Wellness-based interventions, including exercise and nutrition, have been associated with improvements in physical and mental health among this population. This study explores the acceptability, feasibility, and efficacy of a 3-month health and fitness program for veterans.

Materials and Methods

Participants in 2 time-based cohorts from 2019 to 2023 (cohort 1: n = 261; cohort 2: n = 256) were cleared by a physician to participate. Participants then completed a fitness test and self-reported surveys (e.g., quality of life, sleep, and pain) before and after the 3-month program. Participants were recruited to participate at one of three sites: Boston, MA Fort Myers, FL, or Tampa, FL. The 3-month program consisted of weekly, supervised group fitness and one-on-one sessions, nutritional consultations, yoga, and other wellness activities. Primary program outcomes were measured by fitness assessments, self-report surveys, program completion, and program satisfaction. Fitness assessments included measures of weight, body mass index, grip strength, waist to hip ratio, body fat, lean mass, fat mass, heart rate, and blood pressure (BP). Self-report measures included quality of life, depression, loneliness, sleep quality, pain intensity, and pain interference.

Results

In cohort 1, significant improvements were found for measures of weight (P = .01), left-handed grip strength (P < .01), body fat percent (P < .01), and quality of life (P < .01). In cohort 2, significant improvements were found for measures of waist:hip ratio (P = .02), right and left-handed grip strength (P < .01), body mass index (P = .02), body fat percent (P < .01), and quality of life (P = .02). For both cohorts, pain intensity (cohort 1: P = .01, cohort 2: P < .001) and pain interference (cohort 1: P = .02, cohort 2: P < .001) increased significantly.

Conclusions

These data suggest that a 3-month health and fitness program for veterans is acceptable and feasible and may improve physical and mental health outcomes. Considerations for program retention and assessment completion are discussed.
Schopenhauer on the Futility of Suicide
Authors: Marshall Colin
Published: May 2024

Schopenhauer repeatedly claims that suicide is both foolish and futile. But while many commentators express sympathy for his charge of foolishness, most regard his charge of futility as indefensible even within his own system. In this paper, I offer a defence of Schopenhauer’s futility charge, based on metaphysical and psychological considerations. On the metaphysical front, Schopenhauer’s view implies that psychological connections extend beyond the death of an individual. Drawing on Parfit’s discussion of personal identity, I argue that those connections have personal significance, such that suicide does not allow one, as Hamlet hopes, simply ‘not to be’. On the psychological front, I argue that a distinction between agents’ intentions and underlying desires makes room for Schopenhauer’s claim that paradigmatic suicidal agents ultimately desire the opposite of what suicide accomplishes. I conclude by showing how this understanding of futility can buttress Schopenhauer’s charge of foolishness. My interpretation still leaves Schopenhauer vulnerable to certain objections, but shows that his account is more defensible than previous commentators have realized.
Diversity and Molecular Evolution of Nonvisual Opsin Genes across Environmental, Developmental, and Morphological Adaptations in Frogs
Authors: Boyette John L , Bell Rayna C , Fujita Matthew K , Thomas Kate N , Streicher Jeffrey W , Gower David J , Schott Ryan K
Published: May 2024

Nonvisual opsins are transmembrane proteins expressed in the eyes and other tissues of many animals. When paired with a light-sensitive chromophore, nonvisual opsins form photopigments involved in various nonvisual, light-detection functions including circadian rhythm regulation, light-seeking behaviors, and seasonal responses. Here, we investigate the molecular evolution of nonvisual opsin genes in anuran amphibians (frogs and toads). We test several evolutionary hypotheses including the predicted loss of nonvisual opsins due to nocturnal ancestry and potential functional differences in nonvisual opsins resulting from environmental light variation across diverse anuran ecologies. Using whole-eye transcriptomes of 81 species, combined with genomes, multitissue transcriptomes, and independently annotated genes from an additional 21 species, we identify which nonvisual opsins are present in anuran genomes and those that are also expressed in the eyes, compare selective constraint among genes, and test for potential adaptive evolution by comparing selection between discrete ecological classes. At the genomic level, we recovered all 18 ancestral vertebrate nonvisual opsins, indicating that anurans demonstrate the lowest documented amount of opsin gene loss among ancestrally nocturnal tetrapods. We consistently found expression of 14 nonvisual opsins in anuran eyes and detected positive selection in a subset of these genes. We also found shifts in selective constraint acting on nonvisual opsins in frogs with differing activity periods, habitats, distributions, life histories, and pupil shapes, which may reflect functional adaptation. Although many nonvisual opsins remain poorly understood, these findings provide insight into the diversity and evolution of these genes across anurans, filling an important gap in our understanding of vertebrate opsins and setting the stage for future research on their functional evolution across taxa.
SimRNAweb v2.0: a web server for RNA folding simulations and 3D structure modeling, with optional restraints and enhanced analysis of folding trajectories
Authors: Moafinejad S Naeim , de Aquino Belisa R H , Boniecki Michał J , Pandaranadar Jeyeram Iswarya P N , Nikolaev Grigory , Magnus Marcin , Farsani Masoud Amiri , Badepally Nagendar Goud , Wirecki Tomasz K , Stefaniak Filip , Bujnicki Janusz M
Published: May 2024

Research on ribonucleic acid (RNA) structures and functions benefits from easy-to-use tools for computational prediction and analyses of RNA three-dimensional (3D) structure. The SimRNAweb server version 2.0 offers an enhanced, user-friendly platform for RNA 3D structure prediction and analysis of RNA folding trajectories based on the SimRNA method. SimRNA employs a coarse-grained model, Monte Carlo sampling and statistical potentials to explore RNA conformational space, optionally guided by spatial restraints. Recognized for its accuracy in RNA 3D structure prediction in RNA-Puzzles and CASP competitions, SimRNA is particularly useful for incorporating restraints based on experimental data. The new server version introduces performance optimizations and extends user control over simulations and the processing of results. It allows the application of various hard and soft restraints, accommodating alternative structures involving canonical and noncanonical base pairs and unpaired residues, while also integrating data from chemical probing methods. Enhanced features include an improved analysis of folding trajectories, offering advanced clustering options and multiple analyses of the generated trajectories. These updates provide comprehensive tools for detailed RNA structure analysis. SimRNAweb v2.0 significantly broadens the scope of RNA modeling, emphasizing flexibility and user-defined parameter control. The web server is available at https://genesilico.pl/SimRNAweb.