bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence on the temporomandibular joint induced by mandibular malpositioning caused by vertical dimension elevation and occlusal loss in adult rats: An imaging, histological and immunohistochemical study
Authors: Wang Yue , Gao Wenmo , Liang Chao , Jia Fangwen , Geng Wei
Published: May 2024

Background

Mandibular malpositioning may result in an abnormal concentration of stresses within the temporomandibular joint (TMJ) in adult rats, which may further lead to a series of pathological changes, such as articular cartilage wear, subchondral bone sclerosis and osteophyte formation. However, the pathological and adaptive changes in condylar cartilage caused by different stress distributions are still controversial.

Objective

The aim of this study was to observe the effect of sagittal changes in mandibular position on condylar cartilage by changing the occlusal vertical dimension (OVD) in adult rats.

Methods

Fifteen‐week‐old female rats were divided into three groups: control (CON), increased OVD (iOVD) and loss of occlusion (LO) groups. An occlusal plate and tooth extraction were used to establish the animal model. TMJ samples of the experimental and CON groups were observed and investigated by bone morphological, histomorphological and immunohistochemical staining analyses at 3 days, 1 week, 2 weeks, 4 weeks and 8 weeks. Weight curves were plotted.

Results

Micro‐computed tomography showed that, compared with the CON group, cartilage destruction followed by repair occurred in both experimental groups, which was similar to the trend observed in haematoxylin‐eosin staining. All experimental results for the iOVD group showed an approximately similar time trend. Compared with the iOVD group, the toluidine blue and immunohistochemical staining results in the LO group showed no obvious change trend over time.

Conclusion

Compared with occlusal loss, an increase in OVD caused faster and more severe damage to condylar cartilage, and subchondral bone repair occurred later.
REM sleep behaviour disorder (RBD): Personal perspectives and research priorities
Authors: Schenck Carlos H.
Published: May 2024

The formal identification and naming of rapid eye movement (REM) sleep behaviour disorder (RBD) in 1985–1987 is described; the historical background of RBD from 1966 to 1985 is briefly discussed; and RBD milestones are presented. Current knowledge on RBD is identified with reference to recent comprehensive reviews, allowing for a focus on research priorities for RBD: factors and predictors of neurodegenerative phenoconversion from isolated RBD and patient enrolment in neuroprotective trials; isolated RBD clinical research cohorts; epidemiology of RBD; traumatic brain injury, post‐traumatic stress disorder, RBD and neurodegeneration; depression, RBD and synucleinopathy; evolution of prodromal RBD to neurodegeneration; gut microbiome dysbiosis and colonic synuclein histopathology in isolated RBD; other alpha‐synuclein research in isolated RBD; narcolepsy‐RBD; dreams and nightmares in RBD; phasic REM sleep in isolated RBD; RBD, periodic limb movements, periodic limb movement disorder pseudo‐RBD; other neurophysiology research in RBD; cardiac scintigraphy (123I‐MIBG) in isolated RBD; brain magnetic resonance imaging biomarkers in isolated RBD; microRNAs as biomarkers in isolated RBD; actigraphic, other automated digital monitoring and machine learning research in RBD; prognostic counselling and ethical considerations in isolated RBD; and REM sleep basic science research. RBD research is flourishing, and is strategically situated at an ever‐expanding crossroads of clinical (sleep) medicine, neurology, psychiatry and neuroscience.
Courts against backsliding: Lessons from Latin America
Authors: Gamboa Laura , García‐Holgado Benjamín , González‐Ocantos Ezequiel
Published: May 2024

The recent wave of autocratization in Latin America has put courts at the center of debates about regime and regime change. Much of the literature on the judicial politics of democratic backsliding focuses on incumbents' efforts to capture judiciaries and weaponize them against the regime. Our approach is different. We provide illustrations of independent courts in Argentina, Colombia and Mexico that successfully fought back when presidents pushed for reforms that jeopardized democratic stability. With the goal of furthering our knowledge of how judges can also complicate autocratization, the paper thus focuses on a type of horizontal accountability intervention that we refer to as “constitutional balancing.” We also shed light on the reasons why constitutional balancing is well‐equipped to slow down or stop backsliding via a comparison with another type of horizontal accountability intervention: public administration policing. These interventions are increasingly common in Latin America, usually in the form of high‐profile corruption prosecutions. Unlike constitutional balancing, however, public administration policing has proven highly disruptive, and ultimately unable to settle regime‐threatening political conflict.
Cryptic hybridization between the ancient lineages of Natterer's bat (Myotis nattereri)
Authors: Josić Darija , Çoraman Emrah , Waurick Isabelle , Franzenburg Sören , Ancillotto Leonardo , Bajić Branka , Budinski Ivana , Dietz Christian , Görföl Tamás , Hayden Bofill Sofia I. , Presetnik Primož , Russo Danilo , Spada Martina , Zrnčić Vida , Blom Mozes P. K. , Mayer Frieder
Published: May 2024

Studying hybrid zones that form between morphologically cryptic taxa offers valuable insights into the mechanisms of cryptic speciation and the evolution of reproductive barriers. Although hybrid zones have long been the focus of evolutionary studies, the awareness of cryptic hybrid zones increased recently due to rapidly growing evidence of biological diversity lacking obvious phenotypic differentiation. The characterization of cryptic hybrid zones with genome‐wide analysis is in its early stages and offers new perspectives for studying population admixture and thus the impact of gene flow. In this study, we investigate the population genomics of the Myotis nattereri complex in one of its secondary contact zones, where a putative hybrid zone is formed between two of its cryptic lineages. By utilizing a whole‐genome shotgun sequencing approach, we aim to characterize this cryptic hybrid zone in detail. Demographic analysis suggests that the cryptic lineages diverged during the Pliocene, c. 3.6 million years ago. Despite this ancient separation, the populations in the contact zone exhibit mitochondrial introgression and a considerable amount of mixing in nuclear genomes. The genomic structure of the populations corresponds to geographic locations and the genomic admixture changes along a geographic gradient. These findings suggest that there is no effective hybridization barrier between both lineages, nevertheless, their population structure is shaped by dispersal barriers. Our findings highlight how such deeply diverged cryptic lineages can still readily hybridize in secondary contact.
Preferences for livestock bedding as a development substrate of the stable fly, Stomoxys calcitransL. (Diptera: Muscidae), and potential application of entomopathogenic nematodes for controlling stable fly larvae
Authors: Khwanket Niyaporn , Tainchum Krajana , Chareonviriyaphap Theeraphap , Ngoen‐Klan Ratchadawan , Noosidum Atirach
Published: May 2024

The stable fly, Stomoxys calcitrans L. (Diptera: Muscidae), is a significant insect pest with global veterinary implications due to its capacity to both cause nuisance and transmit disease‐causing pathogens to livestock. This study aimed to determine the livestock bedding preferred for use as a development substrate by S. calcitrans larvae and field‐collected adults. The result showed that S. calcitrans larvae exhibited a preference (26.7%) for 7‐day‐old cow manure. Gravid females displayed a pronounced preference (55.0%) for fresh cow manure. As there were eight choices, indifference would result in 12.5% for each bedding substrate. Furthermore, the efficacy of four entomopathogenic nematodes (EPNs), namely Heterorhabditis bacteriophora (Poinar), Heterorhabditis indica Poinar, Karunakar & David (Rhabditida: Heterorhabditidae), Steinernema siamkayai Poinar, Karunakar & David and Steinernema carpocapsae (Weiser) (Rhabditida: Steinernematidae), against S. calcitrans larvae and the persistence after application to livestock bedding substrates were evaluated under laboratory conditions. In filter paper bioassays, all four EPNs caused 76.7%–100.0% mortality in the second instar larvae of S. calcitrans when applied at 50 and 100 infective juveniles (IJs)/cm2 within 5 days after exposure. For the third instar larvae of S. calcitrans, only H. indica induced high mortalities of 86.6% when applied at 100 IJs/cm2 within 5 days after exposure, while the other EPNs resulted in mortalities of less than 70%. The data further demonstrated that H. bacteriophora, H. indica and S. siamkayai remained present in the substrates linked to S. calcitrans larvae for as long as 7 days after the application of EPNs. This study demonstrates the potential of EPNs as a biologically based control agent against larvae of S. calcitrans, a serious pest and significant vector for various livestock animals.
Chronic pulmonary aspergillosis incidence in newly detected pulmonary tuberculosis cases during follow‐up
Authors: Jha Dhouli , Kumar Umesh , Meena Ved Prakash , Sethi Prayas , Singh Amandeep , Nischal Neeraj , Jorwal Pankaj , Vyas Surabhi , Singh Gagandeep , Xess Immaculata , Singh Urvashi B. , Sinha Sanjeev , Mohan Anant , Wig Naveet , Kabra Sushil Kumar , Ray Animesh
Published: May 2024

Background

Chronic pulmonary aspergillosis (CPA) is known to complicate patients with post‐tubercular lung disease. However, some evidence suggests that CPA might co‐exist in patients with newly‐diagnosed pulmonary tuberculosis (P.TB) at diagnosis and also develop during therapy. The objective of this study was to confirm the presence of CPA in newly diagnosed P.TB at baseline and at the end‐of‐TB‐therapy.

Materials and Methods

This prospective longitudinal study included newly diagnosed P.TB patients, followed up at third month and end‐of‐TB‐therapy with symptom assessment, anti‐Aspergillus IgG antibody and imaging of chest for diagnosing CPA.

Results

We recruited 255 patients at baseline out of which 158 (62%) completed their follow‐up. Anti‐Aspergillus IgG was positive in 11.1% at baseline and 27.8% at end‐of‐TB‐therapy. Overall, proven CPA was diagnosed in 7% at baseline and 14.5% at the end‐of‐TB‐therapy. Around 6% patients had evidence of aspergilloma in CT chest at the end‐of‐TB‐therapy.

Conclusions

CPA can be present in newly diagnosed P.TB patients at diagnosis and also develop during anti‐tubercular treatment. Patients with persistent symptoms or developing new symptoms during treatment for P.TB should be evaluated for CPA. Whether patients with concomitant P.TB and CPA, while receiving antitubercular therapy, need additional antifungal therapy, needs to be evaluated in future studies.
Antifungal activity of aminopyrrolnitrin against Trichophyton verrucosum in a guinea pig model of dermatophytosis
Authors: Lee Han Gyu , Bok Eun‐Yeong , Jung Young‐Hun , Hur Tai‐Young , Kim Young‐Ok , Kong Hee Jeong , Kim Dong‐Gyun , Kim Young‐Sam , Oem Jae Ku
Published: May 2024

Background

Dermatophytosis is a common and major public health concern worldwide. Despite the increasing availability of antifungal drugs, relapses and untreated cases of dermatophyte infections are reported. Therefore, novel antifungal agents are required. Aminopyrrolnitrin (APRN) shows promise for dermatophytosis treatment because of its antifungal activity.

Objectives

This study aimed to assess the antifungal properties of APRN against Trichophyton verrucosum (T. verrucosum), in both laboratory settings and a guinea pig model.

Methods

The minimum inhibitory concentrations (MICs) of APRN and enilconazole against T. verrucosum were determined according to the CLSI M38 method. The skins of 16 male guinea pigs were infected with 1.0 × 108 conidia of T. verrucosum and the animals were grouped into sets of four: negative control group (NC) received normal saline; positive control group (PC) received 2 μg/mL of enilconazole; and APRN4 and APRN8 received 4 and 8 μg/mL of APRN, respectively. Clinical, mycological and histological efficacies were measured after 10 days.

Results

The MIC90 of APRN and enilconazole against T. verrucosum was 4 and 2 μg/mL, respectively. The clinical scores of PC, APRN4, and APRN8 were significantly lower than those of NC. Clinical and mycological efficacies were higher for APRN8, APRN4 and PC. No fungi were observed in the skin tissues of APRN4 and APRN8, while fungi were observed in 50% of the PC.

Conclusion

APRN showed antifungal activity against T. verrucosum in vitro and in vivo and is a potential candidate for the treatment of dermatophytosis.
Accurate and comprehensive evaluation of O6‐methylguanine‐DNA methyltransferase promoter methylation by nanopore sequencing
Authors: Halldorsson Skarphedinn , Nagymihaly Richard Mark , Patel Areeba , Brandal Petter , Panagopoulos Ioannis , Leske Henning , Lund‐Iversen Marius , Sahm Felix , Vik‐Mo Einar O.
Published: May 2024

Aims

The methylation status of the O6‐methylguanine‐DNA methyltransferase (MGMT) promoter region is essential in evaluating the prognosis and predicting the drug response in patients with glioblastoma. In this study, we evaluated the utility of using nanopore long‐read sequencing as a method for assessing methylation levels throughout the MGMT CpG‐island, compared its performance to established techniques and demonstrated its clinical applicability.

Methods

We analysed 165 samples from CNS tumours, focusing on the MGMT CpG‐island using nanopore sequencing. Oxford Nanopore Technologies (ONT) MinION and PromethION flow cells were employed for single sample or barcoded assays, guided by a CRISPR/Cas9 protocol, adaptive sampling or as part of a whole genome sequencing assay. Methylation data obtained through nanopore sequencing were compared to results obtained via pyrosequencing and methylation bead arrays. Hierarchical clustering was applied to nanopore sequencing data for patient stratification.

Results

Nanopore sequencing displayed a strong correlation (R2 = 0.91) with pyrosequencing results for the four CpGs of MGMT analysed by both methods. The MGMT‐STP27 algorithm's classification was effectively reproduced using nanopore data. Unsupervised hierarchical clustering revealed distinct patterns in methylated and unmethylated samples, providing comparable survival prediction capabilities. Nanopore sequencing yielded high‐confidence results in a rapid timeframe, typically within hours of sequencing, and extended the analysis to all 98 CpGs of the MGMT CpG‐island.

Conclusions

This study presents nanopore sequencing as a valid and efficient method for determining MGMT promotor methylation status. It offers a comprehensive view of the MGMT promoter methylation landscape, which enables the identification of potentially clinically relevant subgroups of patients. Further exploration of the clinical implications of patient stratification using nanopore sequencing of MGMT is warranted.
Validity of dietary assessment methods compared with doubly labeled water in children: A systematic review and meta‐analysis
Authors: Mehranfar Sanaz , Jalilpiran Yahya , Jafari Alireza , Jayedi Ahmad , Shab‐bidar Sakineh , Speakman John R. , Djafarian Kurosh
Published: May 2024

Objectives

We aimed to validate dietary assessment methods against the gold standard, doubly labeled water (DLW), for estimating total energy intake (TEI).

Methods

PubMed, Scopus, Web of Science, and Google Scholar databases were searched until May 2023. Inclusion criteria encompassed studies involving participants aged 1–18 years, employing dietary assessment methods like food records, dietary histories, food frequency questionnaire (FFQ), or 24‐h recalls estimating TEI alongside DLW to measure total energy expenditure (TEE). Data were pooled using random‐effects meta‐analysis models.

Results

Thirty‐three studies were identified, with sample sizes ranging from 9 to 118 participants. Meta‐analysis of 22 studies identified underestimation of TEI (mean difference [MD] = −262.9 kcal/day [95% CI: −380.0, −145.8]; I2 = 93.55%) for food records compared with TEE estimated by DLW. Other dietary assessment methods, including food recalls (n = 9) (MD = 54.2 kcal/day [95% CI: −19.8, 128.1]; I2 = 49.62%), FFQ (n = 7) (MD = 44.5 kcal/day [95% CI: −317.8, 406.8]; I2 = 94.94%), and diet history (n = 3) (MD = −130.8 kcal/day [95% CI: −455.8, 194.1]; I2 = 77.48%), showed no significant differences in TEI compared with DLW‐estimated TEE. All studies were of high quality.

Conclusion

Food records may underestimate TEI, yet additional research is needed to identify the most accurate methods for assessing children's dietary intake.
A Novel Internal Fixation Design for the Treatment of AO/OTA‐31A3.3 Intertrochanteric Fractures: Finite Element Analysis
Authors: Chen Xiaofeng , Tang Miaotian , Zhang Xiaomeng , Zhang Yichong , Wang Yilin , Xiong Chen , Ji Yun , Wang Yanhua , Zhang Dianying
Published: May 2024

Objective

AO/OTA 31‐A3.3 intertrochanteric fracture is the most unstable type of intertrochanteric fracture, with a high rate of postoperative complications and implant failure. We have designed a new intramedullary fixation, proximal femoral totally bionic nail (PFTBN), for the treatment of A3.3 intertrochanteric fracture. To test its biomechanical performance, we adopted the method of finite element analysis and compared PFTBN with proximal femoral nail antirotation (PFNA) and proximal femoral bionic nail (PFBN, another internal fixation we previously designed for stable intertrochanteric fractures).

Methods

Mimics, 3‐matic, ANSYS, and other software were used to construct a highly precise and realistic 3D digital model of the human femur. An AO/OTA 31‐A3.3 intertrochanteric fracture of the femur was constructed according to the 2018 classification of AO/OTA, and then assembled with PFNA, PFBN and PFTBN models, respectively. The stress distribution and displacement distribution of the three groups of constructs were tested under three times the body weight load and one‐foot standing configuration.

Results

In terms of maximum stress and maximum displacement, the PFTBN group outperforms the PFBN group, and the PFBN group, in turn, surpasses the PFNA group. The maximum stress of PFTBN group was 408.5 Mpa, that of PFBN group was 525.4 MPa, and that of PFNA group was 764.3 Mpa. Comparatively, the maximum stress in the PFTBN group was reduced by 46.6% when contrasted with the PFNA group. Moreover, the stress dispersion within the PFTBN group was more evenly distributed than PFNA group. Regarding maximum displacement, the PFTBN group displayed the least displacement at 5.15 mm, followed by the PFBN group at 7.32 mm, and the PFNA group at 7.73 mm. Notably, the maximum displacement of the PFTBN group was 33.4% less than that observed in the PFNA group. Additionally, the relative displacement between the fragment and implant at the tip of pressure screw or helical blade was 0.22 mm in the PFTBN group, 0.34 mm in the PFBN group, and substantially higher 0.51 mm in the PFNA group.

Conclusion

The “lever‐reconstruction‐balance” theory provides a new perspective for us to understand the mechanical conduction of the proximal femur. Compared with PFNA, in treating A3.3 intertrochanteric fractures PFTBN can better reconstruct the function of lateral wall, restore physiological mechanical conduction, increase postoperative stability, and finally reduce the risk of postoperative cut‐out and implant failure. It might be a better alternative for the treatment of A3.3 intertrochanteric fracture.
Pleiotropic phenotypic effects of the TaCYP78A family on multiple yield‐related traits in wheat
Authors: Ma Meng , Wu Linnan , Li Mengyao , Li Long , Guo Lijian , Ka Deyan , Zhang Tianxing , Zhou Mengdie , Wu Baowei , Peng Haixia , Hu Zhaoxin , Liu Xiangli , Jing Ruilian , Zhao Huixian
Published: May 2024

Increasing crop yield depends on selecting and utilizing pleiotropic genes/alleles to improve multiple yield‐related traits (YRTs) during crop breeding. However, synergistic improvement of YRTs is challenging due to the trade‐offs between YRTs in breeding practices. Here, the favourable haplotypes of the TaCYP78A family are identified by analysing allelic variations in 1571 wheat accessions worldwide, demonstrating the selection and utilization of pleiotropic genes to improve yield and related traits during wheat breeding. The TaCYP78A family members, including TaCYP78A3, TaCYP78A5, TaCYP78A16, and TaCYP78A17, are organ size regulators expressed in multiple organs, and their allelic variations associated with various YRTs. However, due to the trade‐offs between YRTs, knockdown or overexpression of TaCYP78A family members does not directly increase yield. Favourable haplotypes of the TaCYP78A family, namely A3/5/16/17Ap‐Hap II, optimize the expression levels of TaCYP78A3/5/16/17‐A across different wheat organs to overcome trade‐offs and improve multiple YRTs. Different favourable haplotypes have both complementary and specific functions in improving YRTs, and their aggregation in cultivars under strong artificial selection greatly increase yield, even under various planting environments and densities. These findings provide new support and valuable genetic resources for molecular breeding of wheat and other crops in the era of Breeding 4.0.
Organisational teleology 2.0: Grounding biological purposiveness in regulatory control
Authors: Bich Leonardo
Published: May 2024

This paper critically revises the organisational account of teleology, which argues that living systems are first and foremost oriented towards a goal: maintaining their own conditions of existence. It points out some limitations of this account, mainly in the capability to account for the richness and complexity of biological systems and their purposeful behaviours. It identifies the reason of these limitations in the theoretical grounding of this account, specifically in the too narrow notion of closure of constraints, focused on self‐production. It proposes to ground an organisational account of biological teleology in the capability of living system not just to produce and replace their parts, but to control their own internal dynamics and behaviours in such a way as to maintain themselves. This theoretical framework has two advantages. It better captures the distinctive features of biological organisations and consequently the richness and active nature of their purposeful behaviours. By doing so, it makes it possible to apply this framework beyond minimal theoretical models to real biological cases.
Dualism about undercutting defeat
Authors: Tiozzo Marco
Published: May 2024

Most philosophers agree that the distinction between rebutting and undercutting defeaters is sound. Recently, however, there has been much debate over the nature of and relationship between rebutting and undercutting defeaters. Among the things that have been argued about is whether undercutting defeat, in contrast to rebutting defeat, require higher‐order commitment, i.e., a belief regarding the link between the source of justification and the target proposition. This paper examines the debate and argues that whether or not undercutting defeaters require higher‐order commitments to this effect depends on the relevant defeatee at issue. A belief might fail to be rational in at least two ways—either by failing to correctly respond to one's reasons or by failing to be coherent with one's other attitudes. According to dualism about rationality these failings reflect two genuine and distinct kinds of rationality: substantive and structural rationality. In line with this view, the paper suggests that we should make a parallel distinction between substantive and structural undercutting defeaters. An advantage of classifying undercutting defeaters in this way is that it helps to disentangle the current debate. Another interesting result is that the proposed distinction lends further support to dualism about rationality.
Early Family Formation, Selective Migration, and Childhood Conditions in Rural America☆
Authors: Brooks Matthew M. , Clark Shelley
Published: May 2024

Thirty years ago, rural Americans got married and had children at significantly younger ages than urban Americans. More recent data indicate that these differences persist today, but our understanding of what drives these differences remains limited. To address this gap, we (1) generate Kaplan–Meier estimates of the ages of the first marriage, first union, and first birth among those who lived in rural and urban areas in 2019, (2) evaluate the extent to which rural–urban differences in the timing of family formation reflect selective migration, (3) assess whether rural–urban differences in childhood SES and demographic characteristics further explain differences in timing, and (4) explore rural–urban differences by gender. We find substantial 4.3, 3.8, and 5.1‐year gaps in the ages at which rural and urban women marry, start unions, and become parents, respectively. These gaps largely do not reflect selective migration. Differences in women's age of first birth are attributable to differences in childhood conditions, yet differences in marital and union timing remain unexplained. Rural–urban gaps in the timing of family formation are much larger among women than among men. These patterns of early family formation in rural America have critical implications for families' and children's well‐being as well as rural depopulation.
The reach of decentralized poverty governance: Race, politics, and framing poverty in community action agency mission statements
Authors: Kane Emily W.
Published: May 2024

The literature on decentralized public assistance programs in the United States documents racialized, partisan poverty governance founded on paternalism and individualistic frameworks. This article extends that literature to consider such frameworks in a unique site of poverty governance, Community Action Agencies (CAAs). Established during the War on Poverty in the 1960's, CAAs emphasized “maximum feasible participation” from low‐income citizens, aspiring to participatory models and funding structures that some believed could block systemically racist and politicized resource allocation. Drawing on a novel dataset of mission statements for CAAs across the US, I test how three distinct dimensions of the framing of poverty vary by the racial and partisan context of each agency's geographic location. Individualist, passive framings are common, and significantly more so in geographic areas with more residents of color and greater support for Republican political candidates. But some of the inclusive and participatory aspirations of CAA structures remain evident too, with race and politics predicting these even more strongly. Thus, my analyses provide new evidence for the way decentralization allows the deep reach of racialized and partisan approaches to addressing poverty, even with new measures and even in an arena in which inclusive participation was a central founding aspiration.
Tonal Phonotactics in Southern Min
Authors: Huang Yishan
Published: May 2024

This paper is the first to explore tonal phonotactics in the world's natural languages. Zhangzhou Southern Min is theoretically assumed to have 7320 possible syllables but more than 71% of them are not empirically attested. Each lexical tone is logically possible to generate 915 syllables; however, the attested number only ranges from 98 syllables under tone 8 to 392 under tone 1. This study bases on a large corpus to explore how individual tones behave in the formation of attestable syllables, in what way tonal phonotactics occur and what mechanisms have trigged phonotactic constraints from both synchronic and diachronic factors. This study substantially stretches and advances our knowledge of tonal phonotactics as an important phonology phenomenon in this language. The exploration is supposed to serve as a model for thorough investigations of tonal phonotactics in Sinitic languages, shedding important light on the generalization of areal characteristics in Asia that possess rich and complex tonal contrasts. The study also contributes vital linguistics data to the typology of phonotactics in human languages, while enlightening a research direction of using experimental methods to model phonotactic restrictions in speakers' mental grammar and language practice.
Robot-assisted chirality-tunable acoustic vortex tweezers for contactless, multifunctional, 4-DOF object manipulation
Authors: Li Teng , Li Jiali , Bo Luyu , Bachman Hunter , Fan Bei , Cheng Jiangtao , Tian Zhenhua
Published: May 2024

Robotic manipulation of small objects has shown great potential for engineering, biology, and chemistry research. However, existing robotic platforms have difficulty in achieving contactless, high-resolution, 4-degrees-of-freedom (4-DOF) manipulation of small objects, and noninvasive maneuvering of objects in regions shielded by tissue and bone barriers. Here, we present chirality-tunable acoustic vortex tweezers that can tune acoustic vortex chirality, transmit through biological barriers, trap single micro- to millimeter-sized objects, and control object rotation. Assisted by programmable robots, our acoustic systems further enable contactless, high-resolution translation of single objects. Our systems were demonstrated by tuning acoustic vortex chirality, controlling object rotation, and translating objects along arbitrary-shaped paths. Moreover, we used our systems to trap single objects in regions with tissue and skull barriers and translate an object inside a Y-shaped channel of a thick biomimetic phantom. In addition, we showed the function of ultrasound imaging–assisted acoustic manipulation by monitoring acoustic object manipulation via live ultrasound imaging.
Intratumoral antigen signaling traps CD8
+
T cells to confine exhaustion to the tumor site
Authors: Takahashi Munetomo , So Tsz Y. , Chamberlain-Evans Vitalina , Hughes Robert , Yam-Puc Juan Carlos , Kania Katarzyna , Ruhle Michelle , Mann Tiffeney , Schuijs Martijn J. , Coupland Paul , Naisbitt Dean , Halim Timotheus Y. F. , Lyons Paul A. , Lio Pietro , Roychoudhuri Rahul , Okkenhaug Klaus , Adams David J. , Smith Ken G. C. , Jodrell Duncan I. , Chapman Michael A. , Thaventhiran James E. D.
Published: May 2024

Immunotherapy advances have been hindered by difficulties in tracking the behaviors of lymphocytes after antigen signaling. Here, we assessed the behavior of T cells active within tumors through the development of the antigen receptor signaling reporter (AgRSR) mouse, fate-mapping lymphocytes responding to antigens at specific times and locations. Contrary to reports describing the ready egress of T cells out of the tumor, we find that intratumoral antigen signaling traps CD8
+
T cells in the tumor. These clonal populations expand and become increasingly exhausted over time. By contrast, antigen-signaled regulatory T cell (T
reg
) clonal populations readily recirculate out of the tumor. Consequently, intratumoral antigen signaling acts as a gatekeeper to compartmentalize CD8
+
T cell responses, even within the same clonotype, thus enabling exhausted T cells to remain confined to a specific tumor tissue site.
An exception-reporting approach for wound swab culture: effect on post-report antibiotic initiation
Authors: Bloomfield Max , van der Werff Koen , Todd Sue , Bocacao Marjel , Reed Hamish , Balm Michelle , Blackmore Tim
Published: May 2024

A prior analysis suggested that wound swab culture (WSC) results were driving unnecessary antibiotic use in patients who were not already receiving treatment. As a quality-improvement initiative, our laboratory introduced an “exception-reporting” protocol on 1 March 2023, whereby typical wound pathogens susceptible to recommended empiric therapy (flucloxacillin/cefalexin) were not reported, and a comment was provided, stating no significant resistant organisms had been detected. Full results were available to clinicians on request. Cultures falling outside protocol criteria were reported in the standard fashion. This analysis sought to assess the effect of exception-reporting on post-report antibiotic initiation (PRAI). All community WSC results were matched to antibiotic dispensing records from October 2021 to December 2023. Sampling without treatment pre-report was termed “test and wait” (TaW). Following TaW, PRAI was identified if antibiotics were started within 5 days post-report. There were 1,819 and 764 WSCs received in the pre-change and post-change periods, respectively, where an initial TaW approach had been taken and an organism eligible for exception-reporting had been isolated. In the post-change period, 407 (53.3%) met the criteria and were exception-reported. PRAI occurred in 901 (49.5%) pre-change samples, compared to 102 (25.1%,
P
< 0.01) with exception-reporting. There was no detectable increase in hospitalization or repeat WSC collection in the 30 days following exception-reporting. Exception-reporting was associated with a markedly reduced proportion of patients being initiated on antibiotics following WSC where an organism had been isolated. The naming of organisms in reports appears to drive unnecessary antibiotic prescribing in many patients. These results require confirmation in other jurisdictions.

IMPORTANCE

Wound swab culture is a high-volume test performed in clinical microbiology laboratories. In this analysis, we have shown that an alternative approach to reporting positive wound swab cultures has resulted in a large reduction in post-report antibiotic initiation, suggesting that the current standard method of reporting generates considerable unnecessary antibiotic use. If these findings are replicated elsewhere, wider adoption of this reporting would represent an opportunity for many clinical microbiology laboratories to have a significant impact on community antimicrobial stewardship.
Diversity, evolution, and emergence of fish viruses
Authors: Costa Vincenzo A. , Holmes Edward C.
Published: May 2024

The production of aquatic animals has more than doubled over the last 50 years and is anticipated to continually increase. While fish are recognized as a valuable and sustainable source of nutrition, particularly in the context of human population growth and climate change, the rapid expansion of aquaculture coincides with the emergence of highly pathogenic viruses that often spread globally through aquacultural practices. Here, we provide an overview of the fish virome and its relevance for disease emergence, with a focus on the insights gained through metagenomic sequencing, noting potential areas for future study. In particular, we describe the diversity and evolution of fish viruses, for which the majority have no known disease associations, and demonstrate how viruses emerge in fish populations, most notably at an expanding domestic-wild interface. We also show how wild fish are a powerful and tractable model system to study virus ecology and evolution more broadly and can be used to identify the major factors that shape vertebrate viromes. Central to this is a process of virus-host co-divergence that proceeds over many millions of years, combined with ongoing cross-species virus transmission.
Surveillance and phylogenetic analysis of a pathogenic bacterium candidate in nasal discharge from children
Authors: Fukuda Kazumasa , Haro Kaoru , Yamasaki Kei , Ikegami Hiroaki , Saito Mitsumasa
Published: May 2024

“The infectious organism lurking in human airways (IOLA)” is a candidate pathogenic bacterium detected in bronchoalveolar lavage fluid specimens derived from adult patients with chronic lower respiratory tract infections. Genomic analyses of IOLA have revealed that it possesses the smallest and most AT-rich genome among human-derived bacteria. However, its biological properties remain unclear because no culture method has been established for IOLA. Here, we conducted a large-scale IOLA surveillance study of nasal discharge specimens from children in Japan and investigated the correlation between IOLA detection frequency and patient characteristics. We detected IOLA in 5.4% (103 of 1,920) of pediatric nasal discharge samples. No significant differences were observed in the frequency of detection based on the patient’s background. However, with respect to age, the frequency of detection tended to be significantly high at 2–3 and 6 years old. Phylogenetic analysis revealed five phylotypes in the IOLA 16S rRNA gene sequences, and the sequences detected in adult patients with respiratory infections in a previous study belonged to one of the five phylotypes. The involvement of IOLA in the symptoms is not clear, but IOLA is detected at a relatively high frequency in pediatric nasal discharge. Many subjects with detected IOLA were not always IOLA positive, and IOLA was detected transiently. Our findings suggest that IOLA is horizontally transmitted through groups in nursery and elementary schools, and there are differences in biological characteristics among the IOLA phylotypes.

IMPORTANCE

“The infectious organism lurking in human airways (IOLA)” is a candidate pathogenic bacterium strongly suspected to be infectious to the respiratory tracts of humans and animals. However, a culture method for IOLA has not been established yet, and its properties remain unclear. In this study, IOLA was detected at a relatively high frequency in the nasal discharge of children, and five phylotypes of IOLA were identified. One of these phylotypes was found in the bronchoalveolar lavage fluid from adult patients, suggesting lineage-specific differences in the pathogenicity of IOLA. Moreover, it was suggested that IOLA is horizontally transmitted when children gather in groups such as nursery and elementary schools. These findings strongly indicate that IOLAs have been clinically undetected so far but are spreading among children, with one lineage being involved in respiratory diseases in adults. Examining the presence of IOLA in clinical specimens may help to understand the etiology of respiratory diseases with unknown causes.
Gut and respiratory tract microbiota in children younger than 12 months hospitalized for bronchiolitis compared with healthy children: can we predict the severity and medium-term respiratory outcome?
Authors: Cabrera-Rubio Raul , Calvo Cristina , Alcolea Sonia , Bergia María , Atucha Jorge , Pozo Francisco , Casas Inmaculada , Arroyas María , Collado Maria Carmen , García-García Maria Luz
Published: May 2024

Growing evidence indicates that gut and respiratory microbiota have a potential key effect on bronchiolitis, mainly caused by respiratory syncytial virus (RSV). This was a prospective study of 96 infants comparing infants with bronchiolitis (
n
= 57, both RSV and non-RSV associated) to a control group (
n
= 39). Gut (feces) and respiratory [nasopharyngeal aspirate (NPA)] microbial profiles were analyzed by 16S rRNA amplicon sequencing, and respiratory viruses were identified by PCR. Clinical data of the acute episode and follow-up during the first year after infection were recorded. Pairwise comparisons showed significant differences in the gut (
R
2
= 0.0639,
P
= 0.006) and NPA (
R
2
= 0.0803,
P
= 0.006) microbiota between cases and controls. A significantly lower gut microbial richness and an increase in the NPA microbial diversity (mainly due to an increase in
Haemophilus
,
Streptococcus,
and
Neisseria
) were observed in the infants with bronchiolitis, in those with the most severe symptoms, and in those who subsequently developed recurrent wheezing episodes after discharge. In NPA, the higher microbial richness differed significantly between the control group and the non-RSV bronchiolitis group (
P
= 0.01) and between the control group and the RSV bronchiolitis group (
P
= 0.001). In the gut, the richness differed significantly between the control group and the non-RSV group (
P
= 0.01) and between the control group and the RSV bronchiolitis group (
P
= 0.001), with higher diversity in the RSV group. A distinct respiratory and intestinal microbial pattern was observed in infants with bronchiolitis compared with controls. The presence of RSV was a main factor for dysbiosis. Lower gut microbial richness and increased respiratory microbial diversity were associated with respiratory morbidity during follow-up.

IMPORTANCE

Both the intestinal and respiratory microbiota of children with bronchiolitis, especially those with respiratory syncytial virus infection, are altered and differ from that of healthy children. The microbiota pattern in the acute episode could identify those children who will later have other respiratory episodes in the first year of life. Preventive measures could be adopted for this group of infants.
Detection of
Bartonella
spp. in farmed deer (Artiodactyla: Cervidae) using multiplex assays in the Qinghai-Tibet Plateau, China
Authors: Miao Yu , Guo Wentao , Zhang Wen , Chen Zhizheng , Mian Delan , Li Ruixiao , Xu Ailing , Chen Min , Li Dongmei
Published: May 2024

In this study, we investigated the prevalence of
Bartonella
in deer from Qilian County, Qinghai Province, China. Blood samples were collected from 69 red deer, 40 white-lipped deer, and 27 sika deer. The detection of
Bartonella
spp. has been conducted. The overall prevalence of
Bartonella
was 33.6% (46/135). Species-specific prevalence was 50.72% in red deer (35/69), 20.00% in white-lipped deer (8/40), and 11.11% in sika deer (3/27). There were significant differences in the prevalence rates among the different species of deer. The amplicon sequence comparison revealed a high homology of the ruminant-associated
Bartonella
spp. Nanopore sequencing further confirmed the results.
Bartonella
reads were presented in each of the qPCR-positive samples. Phylogenetic analysis indicated that the
Bartonella
sequences detected in deer blood were closely related to ruminant-borne
Bartonella
spp. In summary, we reported the
Bartonella
prevalence of different deer species in Qinghai, and there were at least one species of ruminant-associated
Bartonella
,
B. schoenbuchensis
.

IMPORTANCE

This is the first report about
Bartonella
infections in the deer population from China. We found that there were two species of
Bartonella
and an unidentified species of
Bartonella
among the unculturing strains carried by these deer populations. We first used Nanopore sequencing to detect
Bartonella
from deer blood samples and indicated that Nanopore sequencing is beneficial to detect pathogens due to its advantage of real-time and high sensitivity.
Functional analysis of the methylerythritol phosphate pathway terminal enzymes IspG and IspH from
Zymomonas mobilis
Authors: Misra Jyotsna , Mettert Erin L. , Kiley Patricia J.
Published: May 2024

Isoprenoids are a diverse family of compounds that are synthesized from two isomeric compounds, isopentenyl diphosphate and dimethylallyl diphosphate. In most bacteria, isoprenoids are produced from the essential methylerythritol phosphate (MEP) pathway. The terminal enzymes of the MEP pathway IspG and IspH are [4Fe-4S] cluster proteins, and in
Zymomonas mobilis,
the substrates of IspG and IspH accumulate in cells in response to O
2
, suggesting possible lability of their [4Fe-4S] clusters. Here, we show using complementation assays in
Escherichia coli
that even under anaerobic conditions,
Z. mobilis
IspG and IspH are not as functional as their
E. coli
counterparts, requiring higher levels of expression to rescue viability. A deficit of the sulfur utilization factor (SUF) Fe-S cluster biogenesis pathway did not explain the reduced function of
Z. mobilis
IspG and IspH since no improvement in viability was observed in
E. coli
expressing the
Z. mobilis
SUF pathway or having increased expression of the
E. coli
SUF pathway. Complementation of single and double mutants with various combinations of
Z. mobilis
and
E. coli
IspG and IspH indicated that optimal growth required the pairing of IspG and IspH from the same species. Furthermore,
Z. mobilis
IspH conferred an O
2
-sensitive growth defect to
E. coli
that could be partially rescued by co-expression of
Z. mobilis
IspG.
In vitro
analysis showed O
2
sensitivity of the [4Fe-4S] cluster of both
Z. mobilis
IspG and IspH. Altogether, our data indicate an important role of the cognate protein IspG in
Z. mobilis
IspH function under both aerobic and anaerobic conditions.

IMPORTANCE

Isoprenoids are one of the largest classes of natural products, exhibiting diversity in structure and function. They also include compounds that are essential for cellular life across the biological world. In bacteria, isoprenoids are derived from two precursors, isopentenyl diphosphate and dimethylallyl diphosphate, synthesized primarily by the methylerythritol phosphate pathway. The aerotolerant
Z. mobilis
has the potential for methylerythritol phosphate pathway engineering by diverting some of the glucose that is typically efficiently converted into ethanol to produce isoprenoid precursors to make bioproducts and biofuels. Our data revealed the surprising finding that
Z. mobilis
IspG and IspH need to be co-optimized to improve flux via the methyl erythritol phosphate pathway in part to evade the oxygen sensitivity of IspH.
Genomic epidemiology of
Streptococcus pyogenes
from pharyngeal and skin swabs in Gabon
Authors: Boutin Sébastien , Arnold Benjamin , Alabi Abraham Sunday , Bélard Sabine , Toepfner Nicole , Nurjadi Dennis
Published: May 2024

The disease burden of
Streptococcus pyogenes
is particularly high in low- and middle-income countries. However, data on the molecular epidemiology of
S. pyogenes
in such regions, especially sub-Saharan Africa, are scarce. To address this, whole-genome sequencing (WGS) of
S. pyogenes
from Gabon was performed to identify transmission clusters and provide valuable genomic data for public repositories. A total of 76
S
.
pyogenes
isolates from 73 patients, collected between September 2012 and January 2013, were characterized by short-read whole-genome sequencing. The predominant emm types were
emm
58.0,
emm
81.2 and
emm
223.0 with 9.2% (7 of 76), 7.9% (6 of 76), and 6.6% (5 of 76), respectively. Single-nucleotide polymorphism analysis revealed 16 putative transmission clusters. Four of these were household transmissions. Four antimicrobial genes (
lmrP
,
tetM
,
tetL
, and
thfT
) were found in the
S. pyogenes
isolates from this study. All strains carried
lmrP
. Of the 76 isolates, 64 (84.2%) carried at least one tetracycline resistance gene (
tetM
or
tetL
). Comparisons with other publicly available African genomic data revealed a significant correlation between geographical location and genetic diversity of
S. pyogenes
, with Gabonese strains showing similarities to those from Kenya and certain Oceanian regions. Our study showed that transmission of
S. pyogenes
can occur at the community/household level and that high-resolution molecular typing is needed to monitor changes in circulating clones and to detect community outbreaks. Advocacy for the adoption of WGS for comprehensive molecular characterization of
S. pyogenes
and data sharing through public repositories should be encouraged to understand the molecular epidemiology and evolutionary trajectory of
S. pyogenes
in sub-Saharan Africa.

IMPORTANCE

The study conducted in Gabon underscores the critical importance of addressing the limited knowledge of the molecular epidemiology of
Streptococcus pyogenes
in low- and middle-income countries, particularly sub-Saharan Africa. Our molecular analysis identified predominant
emm
types and unveiled 16 putative transmission clusters, four involving household transmissions. Furthermore, the study revealed a correlation between geographical location and genetic diversity, emphasizing the necessity for a comprehensive understanding of the molecular epidemiology and evolutionary trajectory of
S. pyogenes
in various regions. The call for advocacy in adopting whole-genome sequencing for molecular characterization and data sharing through public repositories is crucial for advancing our knowledge and implementing effective strategies to combat the spread of
S. pyogenes
in sub-Saharan Africa.