bluuebunny/crossref_metadata_2025 huggingface dataset:
AI-based soundscape analysis: Jointly identifying sound sources and predicting annoyance
Authors: Hou Yuanbo , Ren Qiaoqiao , Zhang Huizhong , Mitchell Andrew , Aletta Francesco , Kang Jian , Botteldooren Dick
Published: November 2023

Soundscape studies typically attempt to capture the perception and understanding of sonic environments by surveying users. However, for long-term monitoring or assessing interventions, sound-signal-based approaches are required. To this end, most previous research focused on psycho-acoustic quantities or automatic sound recognition. Few attempts were made to include appraisal (e.g., in circumplex frameworks). This paper proposes an artificial intelligence (AI)-based dual-branch convolutional neural network with cross-attention-based fusion (DCNN-CaF) to analyze automatic soundscape characterization, including sound recognition and appraisal. Using the DeLTA dataset containing human-annotated sound source labels and perceived annoyance, the DCNN-CaF is proposed to perform sound source classification (SSC) and human-perceived annoyance rating prediction (ARP). Experimental findings indicate that (1) the proposed DCNN-CaF using loudness and Mel features outperforms the DCNN-CaF using only one of them. (2) The proposed DCNN-CaF with cross-attention fusion outperforms other typical AI-based models and soundscape-related traditional machine learning methods on the SSC and ARP tasks. (3) Correlation analysis reveals that the relationship between sound sources and annoyance is similar for humans and the proposed AI-based DCNN-CaF model. (4) Generalization tests show that the proposed model's ARP in the presence of model-unknown sound sources is consistent with expert expectations and can explain previous findings from the literature on soundscape augmentation.
Fish chorus variation in a tropical estuarine environment
Authors: Bittencourt Lis , Barbosa Mariana , Fernandes Myllene , Bisi Tatiana L. , Lailson-Brito José , Azevedo Alexandre F.
Published: November 2023

Fish choruses are still understudied in the Southwestern Atlantic Ocean. Temporal and spatial variation of fish choruses at two sites inside Guanabara Bay were investigated between 2021 and 2022; one sampling site was in a Marine Protected Area (MPA), and the other was in a rocky environment closer to vessel trafficking areas. Acoustic recordings were performed on 17 sampling occasions of 24 h, coupled to a temperature data logger. Long-term spectral averages were employed to determine choruses' start, end, and peak times, and third-octave levels were used to characterize spectral characteristics. Fish sounds were also analyzed and investigated with a principal components analysis. Choruses in the MPA lasted, on average, 4.5 h and had a peak frequency of 547.2 ± 226.6 kHz with a peak level of 104.6 ± 8.7 dB re 1 μPa. In contrast, the rocky site choruses lasted 5.5 h on average and had a peak frequency of 371.7 ± 131.0 Hz with a peak level of 113.4 ± 4.0 dB re 1 μPa. Chorus peak frequency was positively correlated to temperature (r = 0.4). Different types of fish sounds were identified, with some acoustics parameters varying between sites. Results indicate more than one chorusing species that may react to different factors.
Introduction to the special issue on perception and production of sounds in the high-frequency range of human speech
Authors: Jacewicz Ewa , Alexander Joshua M. , Fox Robert A.
Published: November 2023

The frequency range audible to humans can extend from 20 Hz to 20 kHz, but only a portion of this range—the lower end up to 8 kHz—has been systematically explored because extended high-frequency (EHF) information above this low range has been considered unnecessary for speech comprehension. This special issue presents a collection of research studies exploring the presence of EHF information in the acoustic signal and its perceptual utility. The papers address the role of EHF hearing in auditory perception, the impact of EHF hearing loss on speech perception in specific populations and occupational settings, the importance of EHF in speech recognition and in providing speaker-related information, the utility of acoustic EHF energy in fricative sounds, and ultrasonic vocalizations in mice in relation to human hearing. Collectively, the research findings offer new insights and converge in showing that not only is EHF energy present in the speech spectrum, but listeners can utilize EHF cues in speech processing and recognition, and EHF hearing loss has detrimental effects on perception of speech and non-speech sounds. Together, this collection challenges the conventional notion that EHF information has minimal functional significance.
Sports Attitudes in Childhood and Income in Adulthood
Authors: Vanzella-Yang Adam , Domond Pascale , Vitaro Frank , Tremblay Richard E. , Bégin Vincent , Côté Sylvana
Published: November 2023

Research shows that sports participation in youth is associated with earnings in adulthood. However, studies have often relied on self-reported earnings and on single indicators of sports participation. Using large-scale data linked to administrative records, we investigate: (a) whether sports attitudes at age 13 are uniquely related to income at ages 30–36 and (b) whether educational attainment and mental health in early adulthood mediate this association. We find that a one SD increase in sports attitudes is related to a 10% increase in income. This association is not entirely confounded by preexisting and co-occurring risk factors. Educational attainment mediates 22% of the association between sports attitudes and income. Sports attitudes are potentially a form of capital deployed in the pursuit of socioeconomic advantages.
Rock properties and sediment caliber govern bedrock river morphology across the Taiwan Central Range
Authors: Carr Julia C. , DiBiase Roman A. , Yeh En-Chao , Fisher Donald M. , Kirby Eric
Published: November 2023

Feedbacks between surface and deep Earth processes in collisional mountain belts depend on how erosion and topographic relief vary in space and time. One outstanding unknown lies in how rock strength influences bedrock river morphology and thus mountain relief. Here, we quantify boulder cover and channel morphology using uncrewed aerial vehicle surveys along 30 kilometers of bedrock-bound river corridors throughout the Taiwan Central Range where regional gradients in rock properties relate to tectonic history. We find that boulder size systematically increases with increasing metamorphic grade and depth of exhumation. Boulder size correlates with reach-scale channel steepness but does not explain observations of highly variable channel width. Transport thresholds indicate that rivers are adjusted to mobilize boulders and are well in excess of the threshold to transport gravel and cobbles, as previously assumed. The linkage between metamorphic history, boulder size, and channel steepness reveals how rock properties can influence feedbacks between tectonics and topography throughout the life span of a mountain range.
Engineering memory with an extrinsically disordered kinase
Authors: Ripoli Cristian , Dagliyan Onur , Renna Pietro , Pastore Francesco , Paciello Fabiola , Sollazzo Raimondo , Rinaudo Marco , Battistoni Martina , Martini Sara , Tramutola Antonella , Sattin Andrea , Barone Eugenio , Saneyoshi Takeo , Fellin Tommaso , Hayashi Yasunori , Grassi Claudio
Published: November 2023

Synaptic plasticity plays a crucial role in memory formation by regulating the communication between neurons. Although actin polymerization has been linked to synaptic plasticity and dendritic spine stability, the causal link between actin polymerization and memory encoding has not been identified yet. It is not clear whether actin polymerization and structural changes in dendritic spines are a driver or a consequence of learning and memory. Using an extrinsically disordered form of the protein kinase LIMK1, which rapidly and precisely acts on ADF/cofilin, a direct modifier of actin, we induced long-term enlargement of dendritic spines and enhancement of synaptic transmission in the hippocampus on command. The activation of extrinsically disordered LIMK1 in vivo improved memory encoding and slowed cognitive decline in aged mice exhibiting reduced cofilin phosphorylation. The engineered memory by an extrinsically disordered LIMK1 supports a direct causal link between actin-mediated synaptic transmission and memory.
Sparking potential over 1200 V by a falling water droplet
Authors: Li Luxian , Li Xuemei , Deng Wei , Shen Chun , Chen Xinhai , Sheng Han , Wang Xiang , Zhou Jianxin , Li Jidong , Zhu Yinlong , Zhang Zhuhua , Yin Jun , Guo Wanlin
Published: November 2023

Hydrovoltaic technology has achieved notable breakthroughs in electric output via using the moving boundary of electric double layer, but the output voltage induced by droplets is saturated around 350 volts, and the underlying mechanism remains to be further clarified. Here, we show that falling water droplets can stably spark an unprecedented voltage up to 1200 volts within microseconds that they contact an electrode placed on top of an electret surface, approaching the theoretical upper limit. This sparking potential can be explained and described by a comprehensive model considering the water-electrode contact dynamics from both the macroscale droplet spreading and the microscale electric double layer formation, as well as the presence of a circuit capacitance. It is demonstrated that a droplet-induced electric spark is sufficient to directly ionize gas at atmospheric pressure and split water into hydrogen and oxygen, showing wide application potential in fields of green energy and intelligence.
ACD15, ACD21, and SLN regulate the accumulation and mobility of MBD6 to silence genes and transposable elements
Authors: Boone Brandon A. , Ichino Lucia , Wang Shuya , Gardiner Jason , Yun Jaewon , Jami-Alahmadi Yasaman , Sha Jihui , Mendoza Cristy P. , Steelman Bailey J. , van Aardenne Aliya , Kira-Lucas Sophia , Trentchev Isabelle , Wohlschlegel James A. , Jacobsen Steven E.
Published: November 2023

DNA methylation mediates silencing of transposable elements and genes in part via recruitment of the Arabidopsis MBD5/6 complex, which contains the methyl-CpG binding domain (MBD) proteins MBD5 and MBD6, and the J-domain containing protein SILENZIO (SLN). Here, we characterize two additional complex members: α-crystalline domain (ACD) containing proteins ACD15 and ACD21. We show that they are necessary for gene silencing, bridge SLN to the complex, and promote higher-order multimerization of MBD5/6 complexes within heterochromatin. These complexes are also highly dynamic, with the mobility of MBD5/6 complexes regulated by the activity of SLN. Using a dCas9 system, we demonstrate that tethering the ACDs to an ectopic site outside of heterochromatin can drive a massive accumulation of MBD5/6 complexes into large nuclear bodies. These results demonstrate that ACD15 and ACD21 are critical components of the gene-silencing MBD5/6 complex and act to drive the formation of higher-order, dynamic assemblies at CG methylation (meCG) sites.
Motion planning around obstacles with convex optimization
Authors: Marcucci Tobia , Petersen Mark , von Wrangel David , Tedrake Russ
Published: November 2023

From quadrotors delivering packages in urban areas to robot arms moving in confined warehouses, motion planning around obstacles is a core challenge in modern robotics. Planners based on optimization can design trajectories in high-dimensional spaces while satisfying the robot dynamics. However, in the presence of obstacles, these optimization problems become nonconvex and very hard to solve, even just locally. Thus, when facing cluttered environments, roboticists typically fall back to sampling-based planners that do not scale equally well to high dimensions and struggle with continuous differential constraints. Here, we present a framework that enables convex optimization to efficiently and reliably plan trajectories around obstacles. Specifically, we focus on collision-free motion planning with costs and constraints on the shape, the duration, and the velocity of the trajectory. Using recent techniques for finding shortest paths in Graphs of Convex Sets (GCS), we design a practical convex relaxation of the planning problem. We show that this relaxation is typically very tight, to the point that a cheap postprocessing of its solution is almost always sufficient to identify a collision-free trajectory that is globally optimal (within the parameterized class of curves). Through numerical and hardware experiments, we demonstrate that our planner, which we name GCS, can find better trajectories in less time than widely used sampling-based algorithms and can reliably design trajectories in high-dimensional complex environments.
Tension-activated nanofiber patches delivering an anti-inflammatory drug improve repair in a goat intervertebral disc herniation model
Authors: Peredo Ana P. , Gullbrand Sarah E. , Friday Chet S. , Orozco Brianna S. , Dehghani Bijan , Jenk Austin C. , Bonnevie Edward D. , Hilliard Rachel L. , Zlotnick Hannah M. , Dodge George R. , Lee Daeyeon , Engiles Julie B. , Hast Michael W. , Schaer Thomas P. , Smith Harvey E. , Mauck Robert L.
Published: November 2023

Conventional microdiscectomy treatment for intervertebral disc herniation alleviates pain but does not repair the annulus fibrosus, resulting in a high incidence of recurrent herniation and persistent dysfunction. The lack of repair and the acute inflammation that arise after injury can further compromise the disc and result in disc-wide degeneration in the long term. To address this clinical need, we developed tension-activated repair patches (TARPs) for annulus fibrosus repair and local delivery of the anti-inflammatory factor anakinra (a recombinant interleukin-1 receptor antagonist). TARPs transmit physiologic strain to mechanically activated microcapsules embedded within the patch, which release encapsulated bioactive molecules in direct response to spinal loading. Mechanically activated microcapsules carrying anakinra were loaded into TARPs, and the effects of TARP-mediated annular repair and anakinra delivery were evaluated in a goat model of annular injury in the cervical spine. TARPs integrated with native tissue and provided structural reinforcement at the injury site that prevented aberrant disc-wide remodeling resulting from detensioning of the annular fibrosus. The delivery of anakinra by TARP implantation increased matrix deposition and retention at the injury site and improved maintenance of disc extracellular matrix. Anakinra delivery additionally attenuated the inflammatory response associated with TARP implantation, decreasing osteolysis in adjacent vertebrae and preserving disc cellularity and matrix organization throughout the annulus fibrosus. These results demonstrate the therapeutic potential of TARPs for the treatment of intervertebral disc herniation.
Targeting DNA methylation and B7-H3 in RB1-deficient and neuroendocrine prostate cancer
Authors: Yamada Yasutaka , Venkadakrishnan Varadha Balaji , Mizuno Kei , Bakht Martin , Ku Sheng-Yu , Garcia Maria Mica , Beltran Himisha
Published: November 2023

Aberrant DNA methylation has been implicated as a key driver of prostate cancer lineage plasticity and histologic transformation to neuroendocrine prostate cancer (NEPC). DNA methyltransferases (DNMTs) are highly expressed, and global DNA methylation is dysregulated in NEPC. We identified that deletion of DNMT genes decreases expression of neuroendocrine lineage markers and substantially reduced NEPC tumor development and metastasis in vivo. Decitabine, a pan-DNMT inhibitor, attenuated tumor growth in NEPC patient–derived xenograft models, as well as retinoblastoma gene (
RB1
)–deficient castration-resistant prostate adenocarcinoma (CRPC) models compared with
RB1
-proficient CRPC. We further found that DNMT inhibition increased expression of B7 homolog 3 (B7-H3), an emerging druggable target, via demethylation of B7-H3. We tested DS-7300a (i-DXd), an antibody-drug conjugate targeting B7-H3, alone and in combination with decitabine in models of advanced prostate cancer. There was potent single-agent antitumor activity of DS-7300a in both CRPC and NEPC bearing high expression of B7-H3. In B7-H3–low models, combination therapy of decitabine plus DS-7300a resulted in enhanced response. DNMT inhibition may therefore be a promising therapeutic target for NEPC and RB1-deficient CRPC and may sensitize B7-H3–low prostate cancer to DS-7300a through increasing target expression. NEPC and RB1-deficient CRPC represent prostate cancer subgroups with poor prognosis, and the development of biomarker-driven therapeutic strategies for these populations may ultimately help improve patient outcomes.
Identification of a small-molecule Tim-3 inhibitor to potentiate T cell–mediated antitumor immunotherapy in preclinical mouse models
Authors: Ma Shuaiya , Tian Ye , Peng Jiali , Chen Chaojia , Peng Xueqi , Zhao Fabao , Li Zhenyu , Li Mengzhen , Zhao Fangcheng , Sheng Xue , Zong Runzhe , Li Yiquan , Zhang Jiwei , Yu Mingyan , Zhu Qingfen , Tian Xiaoyu , Li Yuyang , Neckenig Markus R. , Liu Huiqing , Zhan Peng , Yue Xuetian , Wu Zhuanchang , Gao Lifen , Liang Xiaohong , Liu Xinyong , Li Chunyang , Ma Chunhong
Published: November 2023

T cell immunoglobulin and mucin-containing molecule 3 (Tim-3), expressed in dysfunctional and exhausted T cells, has been widely acknowledged as a promising immune checkpoint target for tumor immunotherapy. Here, using a strategy combining virtual and functional screening, we identified a compound named ML-T7 that targets the FG-CC′ cleft of Tim-3, a highly conserved binding site of phosphatidylserine (PtdSer) and carcinoembryonic antigen–related cell adhesion molecule 1 (CEACAM1). ML-T7 enhanced the survival and antitumor activity of primary CD8
+
cytotoxic T lymphocytes (CTLs) and human chimeric antigen receptor (CAR) T cells and reduced their exhaustion in vitro and in vivo. In addition, ML-T7 promoted NK cells’ killing activity and DC antigen-presenting capacity, consistent with the reported activity of Tim-3. ML-T7 strengthened DCs’ functions through both Tim-3 and Tim-4, which is consistent with the fact that Tim-4 contains a similar FG-CC′ loop. Intraperitoneal dosing of ML-T7 showed comparable tumor inhibitory effects to the Tim-3 blocking antibody. ML-T7 reduced syngeneic tumor progression in both wild-type and Tim-3 humanized mice and alleviated the immunosuppressive microenvironment. Furthermore, combined ML-T7 and anti–PD-1 therapy had greater therapeutic efficacy than monotherapy in mice, supporting further development of ML-T7 for tumor immunotherapy. Our study demonstrates a potential small molecule for selectively blocking Tim-3 and warrants further study.
Effects of boosting and waning in highly exposed populations on dengue epidemic dynamics
Authors: Aogo Rosemary A. , Zambrana Jose Victor , Sanchez Nery , Ojeda Sergio , Kuan Guillermina , Balmaseda Angel , Gordon Aubree , Harris Eva , Katzelnick Leah C.
Published: November 2023

Sequential infection with multiple dengue virus (DENV) serotypes is thought to induce enduring protection against dengue disease. However, long-term antibody waning has been observed after repeated DENV infection. Here, we provide evidence that highly immune Nicaraguan children and adults (
n
= 4478) experience boosting and waning of antibodies during and after major Zika and dengue epidemics. We develop a susceptible-infected-recovered-susceptible (SIRS-type) model that tracks immunity by titer rather than number of infections to show that boosts in highly immune individuals can contribute to herd immunity, delaying their susceptibility to transmissible infection. In contrast, our model of lifelong immunity in highly immune individuals, as previously assumed, results in complete disease eradication after introduction. Periodic epidemics under this scenario can only be sustained with a constant influx of infected individuals into the population or a high basic reproductive number. We also find that Zika virus infection can boost DENV immunity and produce delays and then surges in dengue epidemics, as observed with real epidemiological data. This work provides insight into factors shaping periodicity in dengue incidence and may inform vaccine efforts to maintain population immunity.
Epidemiology and impact of methicillin-sensitive
Staphylococcus aureus
with β-lactam antibiotic inoculum effects in adults with cystic fibrosis
Authors: Svishchuk J. , Ebbert K. , Waddell B. , Izydorczyk C. , Acosta N. , Somayaji R. , Rabin H. R. , Bjornson C. L. , Lisboa L. , Gregson D. B. , Conly J. M. , Surette M. G. , Parkins M. D.
Published: November 2023

Staphylococcus aureus
is the most prevalent cystic fibrosis (CF) pathogen. Several phenotypes are associated with worsened CF clinical outcomes including methicillin-resistance and small-colony-variants. The inoculum effect (IE) is characterized by reduced β-lactam susceptibility when assessed at high inoculum. The IE associates with worse outcomes in bacteremia and other high-density infections, and may therefore be relevant to CF. The prevalence of IE amongst a CF cohort (age ≥18 years), followed from 2013 to 2016, was investigated. Yearly methicillin-sensitive
S. aureus
(MSSA) isolates were screened at standard (5 × 10
5
CFU/mL) and high (5 × 10
7
CFU/mL) inoculum against narrow-spectrum anti-Staphylococcal β-lactams and those with anti-pseudomonal activity common to CF. A ≥ 4-fold increase in minimum inhibitory concentration between standard and high inoculum defined IE. Isolates underwent
blaZ
sequencing and genotyping and were compared against published genomes. Fifty-six percent (99/177) of individuals had MSSA infection. MSSA was observed at ≥10
5
CFU/mL in 44.8% of entry sputum samples. The prevalence of the IE was 25.0%-cefazolin; 13.5%-cloxacillin; 0%-meropenem; 1.0%-cefepime; 5.2%-ceftazidime; and 34.4%-piperacillin-tazobactam amongst baseline MSSA isolates assessed.
blaZ
A associated with cefazolin IE (
P
= 0.0011), whereas
blaZ
C associated with piperacillin-tazobactam IE (
P
< 0.0001). Baseline demographics did not reveal specific risk factors for IE-associated infections, nor were long-term outcomes different. Herein, we observed the IE in CF-derived MSSA disproportionally for cefazolin and piperacillin-tazobactam and this phenotype strongly associated with underlying
blaZ
genotype. The confirmation of CF being a high density infection, and the identification of high prevalence of MSSA with IE in CF supports the need for prospective pulmonary exacerbation treatment studies to understand the impact of this phenotype.
A preclinical model of TB meningitis to determine drug penetration and activity at the sites of disease
Authors: Lanni Faye , Antilus Sainte Rosleine , Hansen, Mark , Parigi Paul , Kaya Firat , LoMauro Katherine , Siow Bernard , Wilkinson Robert J. , Wasserman Sean , Podell Brendan K. , Gengenbacher Martin , Dartois Véronique
Published: November 2023

Tuberculosis meningitis (TBM) is essentially treated with the first-line regimen used against pulmonary tuberculosis, with a prolonged continuation phase. However, clinical outcomes are poor in comparison, for reasons that are only partially understood, highlighting the need for improved preclinical tools to measure drug distribution and activity at the site of disease. A predictive animal model of TBM would also be of great value to prioritize promising drug regimens to be tested in clinical trials, given the healthy state of the development pipeline for the first time in decades. Here, we report the optimization of a rabbit model of TBM disease induced via inoculation of
Mycobacterium tuberculosis
into the cisterna magna, recapitulating features typical of clinical TBM: neurological deterioration within months post-infection, acid-fast bacilli in necrotic lesions in the brain and spinal cord, and elevated lactate levels in cerebrospinal fluid (CSF). None of the infected rabbits recovered or controlled the disease. We used young adult rabbits, the size of which allows for spatial drug quantitation in critical compartments of the central nervous system that cannot be collected in clinical studies. To illustrate the translational value of the model, we report the penetration of linezolid from plasma into the CSF, meninges, anatomically distinct brain areas, cervical spine, and lumbar spine. Across animals, we measured the bacterial burden concomitant with neurological deterioration, offering a useful readout for drug efficacy studies. The model thus forms the basis for building a preclinical platform to identify improved regimens and inform clinical trial design.
Experimental models for HIV latency and molecular tools for reservoir quantification—an update
Authors: Angamuthu Divyadarshini , Vivekanandan Sandhya , Hanna Luke Elizabeth
Published: November 2023

A major impediment for HIV cure is the ability of the virus to integrate its genome in the form of replication-competent proviral DNA into the cellular genome of the host and remain transcriptionally silent and hidden from the host’s immune defense mechanisms in latent reservoir cells. These latent reservoirs are highly heterogeneous, long-lived cells that are capable of reactivating to restore the viremic stage in virally suppressed individuals upon treatment interruption, thus necessitating life-long antiretroviral treatment. Latency reversal has become one of the most explored therapeutic approaches for eliminating HIV reservoirs and effecting HIV cure. Various aspects governing the establishment, maintenance, and reversal of HIV latency continue to be an enigma and warrant further research. Quantifying the size of the latent reservoir pool is also a challenge as these cells are very few in number and cannot be easily differentiated from uninfected cells. This article provides a comprehensive review of the
in vitro
and
in vivo
models currently available for studying HIV latency as well as the recently developed molecular tools for detection and quantification of latent viral reservoirs.
Multiantigen print immunoassay (MAPIA) for the diagnosis of neurocysticercosis: a single-center diagnostic optimization and accuracy study in Lima, Peru
Authors: Toribio L. , Guzman C. , Noazin S. , Zimic-Sheen A. , Zimic M. , Gonzales I. , Saavedra H. , Pretell E. J. , Bustos J. A. , Handali S. , García H. H. ,   on behalf of The Cysticercosis Working Group in Peru
Published: November 2023

Neurocysticercosis (NCC) is the most common helminthic infection of the human central nervous system. The antibody detection assay of choice is the enzyme-linked immunoelectrotransfer blot assay using lentil-lectin purified parasite antigens (LLGP-EITB, Western blot), an immunoassay with exceptional performance in clinical samples. However, its use is mainly restricted to a few research laboratories because the assay is labor-intensive and requires sophisticated equipment, expertise, and large amounts of parasite material for preparation of reagents. We report a new immunoprint assay (MAPIA) that overcomes most of these barriers. We initially compared the performance of five different antigen combinations in a subset of defined samples in the MAPIA format. After selecting the best-performing assay format (a combination of rGP50 + rT24H + sTs14 antigens), 148 archived serum samples were tested, including 40 from individuals with parenchymal NCC, 40 with subarachnoid NCC, and 68 healthy controls with no evidence of neurologic disease. MAPIA using three antigens (rGP50 + rT24H + sTs14) was highly sensitive and specific for detecting antibodies in NCC. It detected 39 out of 40 (97.5%) parenchymal NCC cases and 40/40 (100%) subarachnoid cases and was negative in 67 out of 68 (98.53%) negative samples. MAPIA using three recombinant and synthetic antigens is a simple and economical tool with a performance equivalent to the LLGP-EITB assay for the detection of specific antibodies to NCC. The MAPIA overcomes existing barriers to adoption of the EITG LLGP and is a candidate for worldwide use.
Developing a faculty support program for fostering enriching undergraduate laboratory experiences under limited resource conditions
Authors: Kulkarni Anuttama
Published: November 2023

Meaningful pedagogical reform requires good faculty training and support programs. Such support is particularly valuable when colleges and universities are trying to bring research and inquiry into the laboratory curricula under resource-limited conditions. In this situation, it may help to extend the scope of the faculty support program to include training for practicing experimental techniques, sustainable networking opportunities, and a space to learn about pedagogical reforms. From this perspective, we share our experience about building a faculty development program for public college teachers who teach undergraduate biology in India. Though we designed the program for low-resource settings, the experiments curated could very well represent core biological concepts typically identified by the international community. The activities and overall design of the program can be useful for initiating pedagogical reform in any college/university where the traditional approach to biology laboratory instruction predominates, and high-end research is not easy to access.
Virus replication in the honey bee parasite,
Varroa destructor
Authors: Damayo James E. , McKee Rebecca C. , Buchmann Gabriele , Norton Amanda M. , Ashe Alyson , Remnant Emily J.
Published: November 2023

The ectoparasitic mite
Varroa destructor
is the leading threat to the health of Western honey bees (
Apis mellifera
) primarily through its action as a vector of viruses. However, it is unclear which of the viruses transmitted by
V. destructor
actively infect and replicate in mites, which could facilitate increased transmission. To better understand the role of
V. destructor
as a vector, we took advantage of differences between bee and mite antiviral RNA interference pathways to identify the host specificity of replicating viruses. We used small RNA sequencing of individual
V. destructor
mites to examine viral small interfering RNA (vsiRNA) profiles of deformed wing virus genotypes (DWV-A and DWV-B), associated with colony declines, as well as nine other viruses present in our samples. We found active replication of six
V. destructor
-associated viruses, including a novel virus, Varroa destructor virus 9 (VDV-9), and replication of two honey bee-associated viruses, including both DWV-A and -B genotypes, confirming that mites are biological vectors for important bee pathogens. We show that the antiviral RNAi response can be used to define the host range of viruses in host-parasite interactions, such as honey bees and their parasites, enabling a better understanding of the role of a vector in the evolution and spread of honey bee pathogens.

IMPORTANCE

The parasitic mite
Varroa destructor
is a significant driver of worldwide colony losses of our most important commercial pollinator, the Western honey bee
Apis mellifera
. Declines in honey bee health are frequently attributed to the viruses that mites vector to honey bees, yet whether mites passively transmit viruses as a mechanical vector or actively participate in viral amplification and facilitate replication of honey bee viruses is debated. Our work investigating the antiviral RNA interference response in
V. destructor
demonstrates that key viruses associated with honey bee declines actively replicate in mites, indicating that they are biological vectors, and the host range of bee-associated viruses extends to their parasites, which could impact virus evolution, pathogenicity, and spread.
Identification of host essential factors for recombinant AAV transduction of the polarized human airway epithelium
Authors: Hao Siyuan , Zhang Xiujuan , Ning Kang , Feng Zehua , Park Soo Yeun , Aksu Kuz Cagla , McFarlin Shane , Richart Donovan , Cheng Fang , Zhang Elizabeth Yan , Zhang-Chen Aaron , Yan Ziying , Qiu Jianming
Published: November 2023

Recombinant (r)AAV2.5T was selected from the directed evolution of an adeno-associated virus (AAV) capsid library in the human airway epithelium (HAE). The capsid gene of rAAV2.5T is a chimera of the N-terminal unique coding sequence of AAV2 VP1 unique (VP1u) and the VP2- and VP3-coding sequences of AAV5 with a single amino acid mutation of A581T. We conducted two rounds of genome-wide CRISPR guide (g)RNA library screening for host factors limiting rAAV2.5T transduction in HeLa S3 cells. The screening identified several genes that are critical for rAAV2.5T, including the previously reported genes
KIAA0319L
,
TM9SF2
,
VPS51
, and
VPS54
, as well as a novel gene
WDR63
. We verified the role of KIAA0319L and WDR63 in rAAV2.5T transduction of polarized HAE by utilizing CRISPR gene knockouts. Although KIAA0319L, a proteinaceous receptor for multiple AAV serotypes, played an essential role in rAAV2.5T transduction of polarized HAE either from the apical or basolateral side, our findings demonstrated that the internalization of rAAV2.5T was independent of KIAA0319L. Importantly, we confirmed that WDR63 is an important player in rAAV2.5T transduction of HAE while not being involved in vector internalization and nuclear entry. Furthermore, we identified that the basal stem cells of HAE can be significantly transduced by rAAV2.5T.

IMPORTANCE

The essential steps of successful gene delivery by recombinant adeno-associated viruses (rAAVs) include vector internalization, intracellular trafficking, nuclear import, uncoating, double-stranded (ds)DNA conversion, and transgene expression. rAAV2.5T has a chimeric capsid of AAV2 VP1u and AAV5 VP2 and VP3 with the mutation A581T. Our investigation revealed that KIAA0319L, the multiple AAV serotype receptor, is not essential for vector internalization but remains critical for efficient vector transduction to human airway epithelia. Additionally, we identified that a novel gene
WDR63
, whose cellular function is not well understood, plays an important role in vector transduction of human airway epithelia but not vector internalization and nuclear entry. Our study also discovered the substantial transduction potential of rAAV2.5T in basal stem cells of human airway epithelia, underscoring its utility in gene editing of human airways. Thus, the knowledge derived from this study holds promise for the advancement of gene therapy in the treatment of pulmonary genetic diseases.
Complete genome sequence of
Pseudomonas veronii
strain OST1911 isolated from oil sand tailing pond water in Alberta, Canada
Authors: Shideler Steven M. , Goff Kira , Gauthier Jeff , Levesque Roger C. , Lewenza Shawn
Published: November 2023

Here, we report the complete genome sequence of
Pseudomonas veronii
strain OST1911, recovered from oil sand process-affected water accumulated in tailing ponds. This water contains numerous organic and inorganic compounds of environmental significance. The genome size is 6,435,955 bp with a G+C content of 61.21%.
Three novel sequencing types from seventeen
Staphylococcus aureus
genomes isolated from dairy cows milk in the Free State Province of South Africa
Authors: Khasapane Ntelekwane George , Kwenda Stanford , Khumalo Zamantungwa Thobeka Happiness , Nkhebenyane Sebolelo Jane , Thekisoe Oriel
Published: November 2023

Staphylococcus aureus
is one of the major pathogens causing bovine mastitis, which results in huge economic losses in the dairy industry worldwide. Here, we report genome sequences of 17
S
.
aureus
strains, with three novel sequencing types (ST8495, ST8500, and ST8501) isolated from the milk of dairy cows with subclinical mastitis.
Draft genome sequence of a mosquito repellent
Bacillus licheniformis
strain Ba1 isolated from desert soil
Authors: Chouati Taha , Maski Soufiane , Melloul Marouane , Ajdig Mohammed , Ouchari Lahcen , Rached Bahia , El Fahime Elmostafa
Published: November 2023

Microbial volatile organic compounds have been shown to affect a wide insect behavior. In this paper, we report the draft genome sequence of
Bacillus licheniformis
strain Ba1 previously isolated from desert soil in Morocco. The assembled and annotated draft genome contains 4,726 coding genes, 6 rRNAs and 97 tRNAs.
Genome-wide CRISPR screen identifies GNE as a key host factor that promotes influenza A virus adsorption and endocytosis
Authors: Ma Tianxin , Niu Shiqi , Wu Zihua , Pan Shenghui , Wang Chenyang , Shi Xiaona , Yan Minghao , Xu Bangfeng , Liu Xingpo , Li Luzhao , Yan Dawei , Teng Qiaoyang , Yuan Chunxiu , Pan Xue , Zhang Zhifei , Duc Hoang Minh , Li Zejun , Liu Qinfang
Published: November 2023

Replication of influenza A virus (IAV) is highly reliant on host cell function, and to identify the key host factor required in the influenza A virus life cycle, a genome-wide CRISPR/Cas9 knockout (KO) screen was conducted in A549 cells infected by H1N1 influenza virus. The results showed that glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase (GNE) plays a crucial role in the replication of influenza A virus, and knockout of the GNE significantly reduced the replication of multiple subtype influenza A viruses in A549 cells, and restoration of the GNE expression in the GNE-knockout cells partially recovered IAV infection. Additionally, overexpression of the GNE in wild-type (WT) cells promoted IAV infection to a certain extent. Further study showed that the GNE is involved in α-2,3- and α-2,6-linked sialic acid (Sia) synthesis, which is the major receptor of the influenza A virus, and the GNE knockout downregulated the α-2,3- and α-2,6-linked sialic acid expression. In summary, the knockout of the GNE inhibits adsorption and endocytosis of IAV. This study provides a new approach to elucidate the replication mechanism of IAV and identifies GNE as a potential target for anti-influenza drug development.

IMPORTANCE

Influenza A virus infection requires the assistance of the host proteins. Glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase (GNE) was identified as an important host factor in influenza A virus infection by genome-wide CRISPR screening. GNE knockout (KO) extensively inhibited the replication of multiple subtype influenza A viruses. It indirectly participated in IAV adsorption and endocytosis by regulating the expression of sialic acid (Sia), the main receptor of IAV. This finding provides novel insights into the replication mechanism of IAV.
Timing of India-Asia collision and significant coupling between them around 51 Ma: Insights from the activation history of the Zhongba-Gyangze thrust in southern Tibet
Authors: Zhao Qi , Yan Yi , Tonai Satoshi , Dilek Yildirim , Zhu Zuofei
Published: November 2023

Constraining the timing of tectonic coupling between converging plates is crucial for understanding the transition from continental subduction to continental collision. In the case of the India-Asia collision, thrusting of an accretionary complex onto the Indian continental margin provides the most direct temporal constraint on the early stages of continental collision, as it represents the most immediate upper-crustal fault system corresponding to plate coupling. Here, we used structural analysis combined with K-Ar dating and hydrogen isotopes of authigenic illite and muscovite to unravel the time-progressive development of the Zhongba-Gyangze thrust (ZGT), which represents a tectonic boundary fault in southern Tibet. Our results suggest that the ZGT evolved from its initiation as a single fault zone infiltrated by metamorphic fluids with high δD values (–47‰ to –55‰) at ca. 80 Ma to multiple deformation localization zones starting around 51 Ma. This latter phase is represented by the development of different generations of authigenic 1 M/1Md illite and significant input of meteoric fluids with δD values ranging from –71‰ to –98‰ through multiple episodes of brittle fault reactivation. A Late Cretaceous tectono-thermal event related to the subduction of a Neotethyan oceanic ridge may have been responsible for the formation of 2M1 illite/muscovite at ca. 80 Ma. The oldest (ca. 51 Ma) 1 M/1Md illite age coincides with the first major pulse of shortening in the upper plate after the initial India-Asia contact. Given the synchronous deceleration of India-Asia convergence, the ca. 51 Ma deformation pulse across the Yarlung-Zangbo suture zone demarcates strong coupling (i.e., the onset of continental collision) between India and Asia at this time.
Monochorionic twin pregnancy in a patient with type III osteogenesis imperfecta: a multidisciplinary challenge
Authors: Lee Kai Wei , Mok May Un Sam , Chai Hui Zhong , Yang Liying
Published: November 2023

A woman with severe type III osteogenesis imperfecta spontaneously conceived a monochorionic, diamniotic twin pregnancy. Due to the severity of her condition, her pregnancy required close follow-up involving a multidisciplinary team, including high-risk obstetricians, anaesthetists, pulmonologists and respiratory therapists. Eventually, the twins were delivered via caesarean section at 26 weeks’ gestation.

We discuss the challenges and considerations in managing her high-risk pregnancy, highlighting the importance of multidisciplinary care in achieving a safe outcome for mother and babies.
First-reported case of vaginal late recurrence of Wilms tumor treated with complete pelvic exenteration
Authors: Pizzuti Giada , Quijano Yolanda , Vicente Emilio , Caruso Riccardo
Published: November 2023

Late relapses of Wilms tumour are extremely uncommon but still represent possible events. Even more rarely Wilms tumours present as extrarenal neoplasms, for which it could be difficult to diagnose and treat them promptly.

We present a unique case of late recurrence of Wilms tumour 16 years after the primary diagnosis, with location in the gynaecological system. The relapse presented as a vaginal mass, and it gradually raised up to involve the majority of pelvic organs. We accurately studied the tumour extension, even realising a 3D preoperative reconstruction, and we managed to evaluate the patient with a multidisciplinary team involving general surgeons, urologists, gynaecologists and plastic surgeons. We finally decided for an extended surgical approach and realised a complete pelvic exenteration. Three months after surgery, the patient is in a good general condition, without major surgical complications and with no radiological signs of pelvic tumour relapse.
Treatment-induced neuropathy of diabetes: challenges in diagnosing neuropathic pain, value of sudomotor function testing
Authors: Abdelhamid Salim , Shabani Majlinda , Russjan Arkadiusz , Tarnutzer Alexander Andrea
Published: November 2023

A patient in his 60s was admitted for an extensive neurological work-up due to progressive asymmetrical, distally pronounced pain in both feet and legs. Conventional pain relievers did not help in pain reduction. A Sudoscan revealed small fibre damage in all extremities indicating an underlying neuropathy. The patient had started insulin treatment around 6 months prior to hospitalisation because of a newly diagnosed late-onset diabetes. Due to a rapid drop in glycated haemoglobin (from over 14% to 6% in 4 months), treatment-induced neuropathy of diabetes (TIND) was hypothesised. On increasing the dose of pregabalin and adding duloxetine, the patient reported improvement of symptoms, which further underlined the suspected diagnosis. Hence, in patients with severe hyperglycaemia, changes in glycaemic control should be stepwise and not rapid; however, to date, no guidelines exist how to avoid TIND.
Synchronous presentation ofETV6::RUNX1fusion positive concordant B-acute lymphoblastic leukaemia in identical twin toddlers
Authors: Khera Sanjeev , Kurup Arjun , Agarwal Samir , Tripathi Preeti
Published: November 2023

Concordant leukaemia in identical twins is rare. The likelihood of concordance of leukaemia in twins is near 100% in infancy, around 10% from 1 to 6 years of age, and rare at a later age with variable latency. Reporting of new cases of concordant leukaemia in twins is encouraged to contribute to data pool of this infrequent but exceptional condition; especially when the theories with respect to evolution, natural history and molecular evidence explaining concordant leukaemia in identical twins are still evolving.

We discuss identical pair of monochorionic twin toddlers who were detected to have pallor and blood investigations revealed pancytopenia. Further work up including bone marrow studies revealed synchronous diagnosis of B-acute lymphoblastic leukaemia (B-ALL) withETV6::RUNX1fusion. Synchronous presentation of concordant leukaemia in identical twins is extremely rare. Index twins are the only second set of twins and first one beyond infantile age with synchronous presentation of B-ALL.
Reversing the trend: a scoping review of health innovation transfer or exchange from low- and middle-income countries to high-income countries
Authors: Ishimwe Marie Consolatrice Sage , Kiplagat Jepchirchir , Kadam Knowlton Arina , Livinski Alicia A , Kupfer Linda E
Published: November 2023

The transfer of innovations from low and middle-income countries (LMICs) to high-income countries (HICs) has received little attention, leaving gaps in the understanding of the process, its benefits and the factors influencing it. This scoping review, part of a National Institutes of Health (NIH) project and the focus for a 2022 NIH-sponsored workshop on Global Health Reciprocal Innovation, sought to identify publications describing health innovations that were researched, developed and implemented in LMICs and adapted to address similar health challenges in HICs. A protocol was writtena prioriand registered on Open Science Framework. Four databases were searched for articles published in English from 2000 to 2022 and described health innovations developed in LMICs and were transferred to HICs. Using Covidence, two reviewers initially screened the title and abstract and then the full text; discrepancies were resolved through discussion. Two reviewers collected the data from each article using Covidence and Microsoft Excel; discrepancies were resolved by a separate third reviewer. 7191 records were retrieved and screened of which 12 studies were included. Various frameworks and methodologies were employed in these studies, with a particular emphasis on adaptation and adoption of innovations. The review uncovered different paradigms of LMIC to HIC innovation transfer and exchange, including unidirectional transfers from LMICs to HICs as well as bidirectional or multidirectional mutually beneficial exchanges. The use of both qualitative and quantitative data collection methods was common across all the included articles. Facilitators for innovation transfers included stakeholder engagement, relevance of local context, simplicity, and sufficient funding, promotion and branding. Barriers to transfers were mostly the opposite of the facilitators. Our results highlighted the underexplored field of LMIC to HIC innovation transfer and exchange and lay the foundation for future research studies.