bluuebunny/crossref_metadata_2025 huggingface dataset:
Cloning, heterologous expression and purification of the novel thermo-alkalistable cellulase from Geobacillus sp. TP-3 and its molecular characterisation
Authors: Arya Meghna , Chauhan Garima , Verma Utsav , Sharma Monica
Published: April 2024

Background

Thermophilic cellulases are essential for effectively degrading cellulose, which is a significant part of lignocellulosic waste. In this study, we focused on a cellulase gene (~ 1.2 kb) obtained from Geobacillus sp. TP-3, a thermo-alkalophilic bacterium isolated from the hot springs of Tapovan (Uttarakhand, India). Cellulase gene (~ 1.2 kb) was amplified via PCR, cloned into pET-28a (+) vector, transferred to Escherichia coli DH5α cells and expressed in Escherichia coli BL21 (DE3). The recombinant cellulase (rCel_TP) was purified using Ni2+-NTA affinity chromatography.

Results

The purified rCel_TP enzyme exhibited optimal activity at 50 ºC and pH 8, displaying stability even after 3 h of incubation at 50 ºC. The molecular weight of the purified 6 × His-tagged rCel_TP was determined to be ~ 40.2 kDa. Under conditions of 50 ºC and pH 8, the kinetic parameters of the purified enzyme were determined, with Km and Vmax values of 116.78 mg/mL and 44.05 µmolmg−1 min−1, respectively. The activity of the rCel_TP cellulase was significantly improved by Hg2+, Cu2+ and Co2+. However, it was suppressed by dithiothreitol and β-mercaptoethanol. Ethylenediaminetetraacetic acid and solvents also had a slight inhibitory effect.

Conclusion

These results suggest the potential applications of the recombinant cellulase in biomass conversion processes for the production of fuels and other industrial operations. The study contributes valuable insights into the properties and applicability of cellulases derived from extremophilic microorganisms.

Graphical abstract
Use of Sodium Thiosulfate as an Otoprotectant in Patients With Cancer Treated With Platinum Compounds: A Review of the Literature
Authors: Meijer Annelot J.M. , Diepstraten Franciscus A. , Ansari Marc , Bouffet Eric , Bleyer Archie , Fresneau Brice , Geller James I. , Huitema Alwin D.R. , Kogner Per , Maibach Rudolf , O'Neill Allison F. , Papadakis Vassilios , Rajput Kaukab M. , Veal Gareth J. , Sullivan Michael , van den Heuvel-Eibrink Marry M. , Brock Penelope R.
Published: April 2024

PURPOSE

Hearing loss occurs in 50%-70% of children treated with cisplatin. Scientific efforts have led to the recent approval of a pediatric formula of intravenous sodium thiosulfate (STS) for otoprotection by the US Food and Drug Administration, the European Medicines Agency, and the Medicines and Health Regulatory Authority in the United Kingdom. To inform stakeholders regarding the clinical utility of STS, the current review summarizes available literature on the efficacy, pharmacokinetics (PK), and safety of systemic STS to minimize cisplatin-induced hearing loss (CIHL).

DESIGN

A comprehensive narrative review is presented.

RESULTS

Thirty-one articles were summarized. Overall, systemic STS effectively reduces CIHL in the preclinical and controlled clinical study settings, in both adults and children with cancer. The extent of CIHL reduction depends on the timing and dosing of STS in relation to cisplatin. Both preclinical and clinical data suggest that systemic STS may affect plasma platinum levels, but studies are inconclusive. Delayed systemic administration of STS, at 6 hours after the cisplatin infusion, does not affect cisplatin-induced inhibition of tumor growth or cellular cytotoxicity in the preclinical setting, nor affect cisplatin efficacy and survival in children with localized disease in the clinical setting.

CONCLUSION

Systemic administration of STS effectively reduces the development and degree of CIHL in both the preclinical and clinical settings. More studies are needed on the PK of STS and cisplatin drug combinations, the efficacy and safety of STS in patients with disseminated disease, and the ability of STS to prevent further deterioration of pre-established hearing loss.
Identification of Eukaryotic Translation Initiation Factor 4B as a Novel Candidate Gene for Congenital Hypothyroidism
Authors: Sun Feng , Zhang Rui-Jia , Fang Ya , Yan Cheng-Yan , Zhang Chang-Run , Wu Feng-Yao , Yang Rui-Meng , Han Bing , Song Huai-Dong , Zhao Shuang-Xia
Published: April 2024

Context

Congenital hypothyroidism (CH) is the most common endocrine disorder in neonates, but its etiology is still poorly understood.

Objective

We performed whole exome sequencing to identify a novel causative gene for CH and functional studies to validate its role in the occurrence of CH.

Methods

Whole exome sequencing in 98 CH patients not harboring known CH candidate genes and bioinformatic analysis were performed. Functional analysis was performed using morpholino, a synthetic short antisense oligonucleotide that contains 25 DNA bases on a methylene morpholine backbone, in zebrafish and CRISPR-Cas9-mediated gene knockout in mice.

Results

Eukaryotic translation initiation factor 4B (EIF4B) was identified as the most promising candidate gene. The EIF4B gene was inherited in an autosomal recessive model, and 1 patient with thyroid dysgenesis carried EIF4B biallelic variants (p.S430F/p.P328L). In zebrafish, the knockdown of eif4ba/b expression caused thyroid dysgenesis and growth retardation. Thyroid hormone levels were significantly decreased in morphants compared with controls. Thyroxine treatment in morphants partially rescued growth retardation. In mice, the homozygous conceptuses of Eif4b+/− parents did not survive. Eif4b knockout embryos showed severe growth retardation, including thyroid dysgenesis and embryonic lethality before E18.5.

Conclusion

These experimental data support a role for EIF4B function in the pathogenesis of the hypothyroid phenotype seen in CH patients. Our work indicates that EIF4B was identified as a novel candidate gene in CH. EIF4B is essential for animal survival, but further studies are needed to validate its role in the pathogenesis of CH.
Molecular Assessment of Proadipogenic Effects for Common-Use Contraceptives and Their Mixtures
Authors: Chiang Yu-Ting Tiffany , Kassotis Christopher D
Published: April 2024

Hormonal contraceptives are widely prescribed due to their effectiveness and convenience and have become an integral part of family planning strategies worldwide. In the United States, approximately 65% of reproductive-aged women are estimated to be using contraceptive options, with approximately 33% using one or a combination of hormonal contraceptives. While these methods have undeniably contributed to improved reproductive health, recent studies have raised concerns regarding their potential effect on metabolic health. Despite widespread anecdotal reports, epidemiological research has been mixed as to whether hormonal contraceptives contribute to metabolic health effects. As such, the goals of this study were to assess the adipogenic activity of common hormonal contraceptive chemicals and their mixtures. Five different models of adipogenesis were used to provide a rigorous assessment of metabolism-disrupting effects. Interestingly, every individual contraceptive (both estrogens and progestins) and each mixture promoted significant adipogenesis (eg, triglyceride accumulation and/or preadipocyte proliferation). These effects appeared to be mediated in part through estrogen receptor signaling, particularly for the contraceptive mixtures, as cotreatment with fulvestrant acted to inhibit contraceptive-mediated proadipogenic effects on triglyceride accumulation. In conclusion, this research provides valuable insights into the complex interactions between hormonal contraceptives and adipocyte development. The results suggest that both progestins and estrogens within these contraceptives can influence adipogenesis, and the specific effects may vary based on the receptor disruption profiles. Further research is warranted to establish translation of these findings to in vivo models and to further assess causal mechanisms underlying these effects.
Multiple Synchronous Spinal Dural Arteriovenous Fistulas: A Systematic Literature Review
Authors: Ikeuchi Yusuke , Fujita Atsushi , Kohta Masaaki , Yamanishi Shunsuke , Tanaka Kazuhiro , Sasayama Takashi
Published: April 2024

BACKGROUND AND OBJECTIVES:

Spinal dural arteriovenous fistulas (SDAVFs) lead to progressive neurological decline with symptoms such as paraparesis, bowel and bladder dysfunction, and sensory disturbances because of impaired spinal cord venous drainage. This study aimed to systematically review the literature on multiple synchronous SDAVFs and present 2 cases from our institution.

METHODS:

A comprehensive search was performed to identify all published cases of multiple synchronous SDAVFs. Overall, 23 patients with multiple synchronous SDAVFs were identified, including 21 from 19 articles and 2 from this study. The clinical presentation, lesion location, radiographic features, surgical treatment, and outcomes were analyzed in each patient.

RESULTS:

All patients in this study were male, and the duration from symptom onset to diagnosis in many of these patients was longer than that previously reported. Previous studies suggested that multiple SDAVFs typically occurred within 3 or fewer vertebral levels. However, >50% of the examined patients had remote lesions separated by more than 3 vertebral levels. Patients with remote lesions had a significantly worse outcome (1/7 vs 8/11, 95% CI 0.001-0.998; P = .049).

CONCLUSION:

Accurately locating fistulas before spinal angiography is critical for managing multiple remote SDAVFs. Considering the possibility of multiple remote SDAVFs, careful interpretation of imaging findings is essential for an accurate diagnosis and appropriate treatment planning.
Two sequential gene expression programs bridged by cell division support long-distance collective cell migration
Authors: Sun Jingjing , Durmaz Ayse Damla , Babu Aswini , Macabenta Frank , Stathopoulos Angelike
Published: April 2024

The precise assembly of tissues and organs relies on spatiotemporal regulation of gene expression to coordinate the collective behavior of cells. In Drosophila embryos, the midgut musculature is formed through collective migration of caudal visceral mesoderm (CVM) cells, but how gene expression changes as cells migrate is not well understood. Here, we have focused on ten genes expressed in the CVM and the cis-regulatory sequences controlling their expression. Although some genes are continuously expressed, others are expressed only early or late during migration. Late expression relates to cell cycle progression, as driving string/Cdc25 causes earlier division of CVM cells and accelerates the transition to late gene expression. In particular, we found that the cell cycle effector transcription factor E2F1 is a required input for the late gene CG5080. Furthermore, whereas late genes are broadly expressed in all CVM cells, early gene transcripts are polarized to the anterior or posterior ends of the migrating collective. We show this polarization requires transcription factors Snail, Zfh1 and Dorsocross. Collectively, these results identify two sequential gene expression programs bridged by cell division that support long-distance directional migration of CVM cells.
Positive and negative durotaxis – mechanisms and emerging concepts
Authors: Mathieu Mathilde , Isomursu Aleksi , Ivaska Johanna
Published: April 2024

Cell migration is controlled by the coordinated action of cell adhesion, cytoskeletal dynamics, contractility and cell extrinsic cues. Integrins are the main adhesion receptors to ligands of the extracellular matrix (ECM), linking the actin cytoskeleton to the ECM and enabling cells to sense matrix rigidity and mount a directional cell migration response to stiffness gradients. Most models studied show preferred migration of single cells or cell clusters towards increasing rigidity. This is referred to as durotaxis, and since its initial discovery in 2000, technical advances and elegant computational models have provided molecular level details of stiffness sensing in cell migration. However, modeling has long predicted that, depending on cell intrinsic factors, such as the balance of cell adhesion molecules (clutches) and the motor proteins pulling on them, cells might also prefer adhesion to intermediate rigidity. Recently, experimental evidence has supported this notion and demonstrated the ability of cells to migrate towards lower rigidity, in a process called negative durotaxis. In this Review, we discuss the significant conceptual advances that have been made in our appreciation of cell plasticity and context dependency in stiffness-guided directional cell migration.
Pulsative venous return from the branchial vessels to the heart of the bivalve Mytilus galloprovincialis supports the constant-volume mechanism
Authors: Seo Eriko , Seo Yoshiteru
Published: April 2024

In bivalves and gastropods, ventricle contraction causes a negative pressure in the auricles and increases venous return from the afferent oblique vein (AOV): the constant-volume (CV) mechanism. The flow in the AOV should be a pulsative flow synchronized with the ventricular contraction. The flow in the heart and adjacent vessels of Mytilus galloprovincialis were measured by magnetic resonance imaging to confirm this hypothesis. Under a regular heartbeat, pulsative flows in the AOV and branchial vessels (BVs) were almost completely synchronized with the flow in the aorta, while filling of the ventricle was in the opposite phase. Flows in the BVs were directed to the posterior direction, and a pair of BVs in the gill axes (the efferent BVs) were connected to the AOV. Based on the images of the whole pathway of the AOV in an oblique slice, we confirmed that haemolymph flow was evoked from the efferent BVs and flow into the ventricle via the auricle was completed in a single heartbeat. Therefore, the walls of the AOV and BVs could resist negative transmural pressure caused by the ventricular contraction. In conclusion, the auricle, the AOV and the BVs, including the gill filaments, act as a suction pump. The pulsative venous return is driven by the negative pressure of the AOV as in the CV mechanism, and the negative pressure in the efferent BVs could draw haemolymph from the sinus via the gill and the afferent BVs. Therefore, Mytilus can start and stop its heartbeat as necessary.
How Hospitals Differentiate Health Information Technology Portfolios for Clinical Care Efficiency: Insights from the HITECH Act
Authors: Pye Jessica , Rai Arun , Dong John Qi
Published: April 2024

Our research reveals the significant impact of evolving policy uncertainty on hospital strategies to mitigate cost-based performance deficits in clinical care processes through differentiation in search for health information technology (HIT). Key for hospital administrators and managers, our findings reveal the benefit of leveraging external benchmarks for performance feedback, enabling strategic, innovative approaches to HIT investments tailored to enhance clinical care efficiency and cost-effectiveness. Moreover, our findings have important implications for healthcare policymakers, highlighting the necessity to consider the varied responses of hospitals to policy fluctuations. Recognizing that hospitals proactively adapt their HIT portfolios in anticipation of new laws, and that these adaptations are most diverse under moderate policy uncertainty, is crucial. This nuanced understanding can guide policymakers in fostering an environment that encourages both the exploration of novel technologies and the widespread adoption of effective solutions across the healthcare spectrum. By bridging the gap between policy development and hospital administration, our work offers a road map for aligning strategic technological differentiation with policy objectives, ultimately enhancing healthcare delivery and outcomes.
Atypical pulmonary metastasis of prostate adenocarcinoma: a rare phenomenon
Authors: Jamil Asma , Ali Ruhma , Paige Amy , Miller Richard , Mistry Nirav , Abbas Ahmed , Taha Abu Tahir
Published: April 2024

Prostate cancer can metastasise to the lung. Most common presentations described in the literature are solitary pulmonary nodules, lymphangitic spread and, rarely, pleural effusion. We describe a case of prostate adenocarcinoma with diffuse bilateral reticulonodular and lymphangitic pulmonary metastasis, and malignant pleural effusion while being on androgen deprivation therapy.
Finite intersection of valuation overrings of polynomial rings in at most three variables
Authors:   University of South Carolina Salkehatchie, Paudel Lokendra
Published: April 2024

The group of divisibility of an integral domainis the multiplicative group of nonzero principal fractional ideals ofthe domain and is a partially ordered group under reverse inclusion. We study the group of divisibility of a finite intersection of valuation overrings of polynomial rings in at most three variables and we classify all semilocal lattice-ordered groups which are realizable over k[x1,x2,...,xn] for n≤3.
Spectral multiplicity functions of adjacency operators of graphs and cospectral infinite graphs
Authors:   Universit ́e de Gen`eve, de la Harpe Pierre
Published: April 2024

The adjacency operator of a graph has a spectrum and a class of scalar-valued spectral measures which have been systematically analyzed; it also has a spectral multiplicity function which has been less studied. The first purpose of this article is to review some examples of infinite graphs for which the spectral multiplicity function of the adjacency operator has been determined. The second purpose of this article is to show explicit examples of infinite connected graphs which are cospectral, i.e., which have unitarily equivalent adjacency operators, and also explicit examples of infinite connected graphs which are uniquely determined by their spectrum.
Feminists for a new Constitution in Chile: forging progressive alliances in times of crisis
Authors: Cruz Melany
Published: April 2024

This article explores the impact and influence of the feminist movement in Chile on the draft of feminist progressive ideas in the Constitutional process of 2021, emerging as a consequence of the social uprising of 2019. Central to this analysis is the pivotal role played by what I term ‘feminists-in-movement’ and ‘feminists-in-power’, delineating the common narratives between grassroots feminist organisations and those individuals advocating within formal political structures, such as political parties and governmental bodies. While the Constitutional draft embodied numerous feminist perspectives, this article focuses on elucidating the feminist political influence by analysing two key proposals included in the 2021 Constitutional draft: care rights and gender-focused politics. The proposals serve as exemplars illustrating the power of political collaboration in pushing progressive agendas during societal upheaval. By dissecting these proposals, this article underlines the significance of forging alliances between different feminist factions, underscoring their collective ability to advance transformative policies during moments of crisis.
Accurate measurement of a THz beam radius through a knife-edge technique with a photoconductive antenna detector
Authors: Morikawa Osamu , Hattori Ai , Yamamoto Kohji , Kurihara Kazuyoshi , Furuya Takashi , Kuwashima Fumiyoshi , Kitahara Hideaki , Tani Masahiko
Published: April 2024

In a terahertz (THz) time-domain spectroscopic system, the THz beam waist radius can be measured by eclipsing the beam waist with a semi-infinite mask while monitoring signal variation (knife-edge technique). However, the obtained beam waist radius is affected by the spatial distribution of the detector sensitivity. This effect was confirmed by calculating the refractive-index corrections required when inserting a sample into the beam waist with and without consideration of the detector sensitivity distribution and comparing them to the experimental results. The real beam waist radius was 2 times larger than that obtained by simply differentiating the signal variation in a system comprising optics symmetrical about the beam waist. This effect must be considered in obtaining the correct THz beam profile by the knife-edge technique.
How is photon-blockade breakdown different from optical bistability? A neoclassical story
Authors: Kurkó Árpád , Német Nikolett , Vukics András
Published: April 2024

The photon-blockade breakdown bistability can be intuitively explained invoking the energy spectrum of the interacting qubit-mode system. Yet, the neoclassical solution of the driven-dissipative Jaynes-Cummings model has been shown to capture several key aspects of the phenomenon. In this paper, we set out to compare a fully quantum solution with the neo- and semiclassical solutions. Although the neoclassical theory is founded on the assumption of a pure partial state for the qubit, it is not simply the γ→0 limit of the semiclassical theory, the semi- versus neoclassical duality being a case of non-commutativity of limits. Furthermore, we show that the neoclassical predictions still hold in the case of a small qubit decay. Tracing the bistable behavior for different detunings, we show that it is robust over a significant range of Δ values. We demonstrate that the aptitude of the neoclassical description is founded on the high quantum purity of the bright state of the photon-blockade breakdown bistability, which sharply differentiates this phenomenology from conventional optical bistability. It is thereby demonstrated that driven-dissipative dynamics can produce closely separable pure steady states in an interacting bipartite.
Multifunctional integrated metamaterials for radar-infrared-visible compatible multispectral stealth
Authors: Meng Zhen , Liu Dongqing , Xu Cuilian , Wang Jiafu , Pang Yongqiang , Yang Jiaheng , Li Xinghua , Gui Boheng , Cheng Haifeng
Published: April 2024

Metamaterials offer exciting opportunities for developing multispectral stealth due to their unique electromagnetic properties. However, currently transparent radar-infrared-visible compatible stealth metamaterials typically involve complex hierarchical designs, leading to thickness and transparency limitations. Here, we propose an integrated metamaterial for multispectral stealth with high transparency. Our design features an ITO/dielectric/ITO sandwich structure, with the upper-layer ITO acting as a resonator for broadband microwave absorption while maintaining a high filling ratio to suppress infrared (IR) radiation. Experimental results demonstrate excellent performance, with over 90% microwave absorption in 8–18 GHz, an IR emissivity of approximately 0.36 in 3–14 µm, an average optical transmittance of 74.1% in 380–800 nm, and a thickness of only 2.4 mm. With its multispectral compatibility, the proposed metamaterial has potential applications in stealth and camouflage fields.
Multiple toroidal dipole Fano resonances from quasi-bound states in the continuum in an all-dielectric metasurface
Authors: Sun Fangxin , Fan Xinye , Fang Wenjing , Zhao Jingjing , Xiao Wenxing , Li Chuanchuan , Wei Xin , Tao Jifang , Wang Yanling , Kumar Santosh
Published: April 2024

In this paper, a highly sensitive sensor consisting of a silicon nanorod and symmetric rings (SNSR) is presented. Theoretically, three Fano resonances with high Q-factors are excited in the near-infrared range by breaking the symmetry structure based on quasi-bound states in the continuum (Q-BICs). The electromagnetic near-field analysis confirms that the resonances are mainly controlled by toroidal dipole (TD) resonance. The structure is optimized by adjusting different geometrical parameters, and the maximum Q-factor of the Fano resonances can reach 7427. To evaluate the sensing performance of the structure, the sensitivity and the figure of merit (FOM) are calculated by adjusting the environmental refractive index: the maximum sensitivity of 474 nm/RIU and the maximum FOM of 3306 RIU-1. The SNSR can be fabricated by semiconductor-compatible processes, which is experimentally evaluated for changes in transmission spectra at different solution concentrations. The results show that the sensitivity and the Q-factor of the designed metasurface can reach 295 nm/RIU and 850, while the FOM can reach 235 RIU-1. Therefore, the metasurface of SNSR is characterized by high sensitivity and multi-wavelength sensing, which are current research hotspots in the field of optics and can be applied to biomedical sensing and multi-target detection.
Tilted Bragg grating in a glycerol-infiltrated specialty optical fiber for temperature and strain measurements
Authors: Hu Xuehao , Liu Yang , Wei Heming , Teng Chuanxin , Yu Qianqing , Luo Zhijun , Lian Zhenggang , Qu Hang , Caucheteur Christophe
Published: April 2024

In this Letter, we propose an in-line tilted fiber Bragg grating sensor for temperature and strain measurements. The grating is inscribed in a specialty optical fiber using tightly focused femtosecond laser pulses and the line-by-line direct writing method. Beside the central core in which the grating is produced, a hollow channel filled with glycerol aqueous solution significantly improves the sensitivity of the fiber cladding modes due to its high thermo-optic coefficient. We show that the temperature sensitivity of the core mode is 9.8 pm/°C, while the one of the cladding modes is strongly altered and can reach −24.3 pm/°C, in the investigated range of 20–40°C. For the strain measurement, sensitivities of the core mode and the cladding modes are similar (∼0.60 pm/με) between 0 and 2400 με. The significative difference of temperature sensitivity between the two modes facilitates the discrimination of the dual parameters in simultaneous measurements.
Optical single-sideband (OSSB) Raman laser system based on an atomic filter for atom gravimeters
Authors: Yi Cong , Zhao Yang , Zhuang Wei , Chen Jingbiao , Shi Tiantian , Qin Xiaomin
Published: April 2024

Phase-modulator-generated laser for Raman transition is widely used in atom gravimeters to simplify a system and improve robustness. However, the induced additional sidebands (ASBs) lead to systematic errors in gravity measurement. This work presents a novel, to our knowledge, method to generate an optical single-sideband (OSSB) laser for Raman transition through phase modulation based on a Faraday anomalous dispersion atomic filter (FADOF). The experimental result indicates that it can reduce the additional sidebands with a signal-to-noise ratio (SNR, the intensity ratio of carrier and unwanted sidebands) of better than 50 dB, and the phase shift caused by ASBs is demonstrated to be effectively suppressed from 358.8 to 2.2 mrad. Furthermore, this system has already been applied on an atom gravimeter to achieve a primary gravity measurement. It shows that the FADOF-based Raman laser system is a new scheme for a compact atom absolute gravimeter.
Vortex phase-based adaptive moiré technique accommodating micro displacement measurement of freeform surfaces
Authors: Zhang Lei , Wang Aoxin
Published: April 2024

The traditional displacement measurement interferometer (DMI) provides elegant performance by straight interference fringe movement counting to convert a phase calculation into an image motion calculation. However, it cannot be applied to a curve surface displacement measurement. The counting of the movement of irregular fringes is not achievable. We provide an adaptive moiré technique with a vortex phase to realize micro displacement measurement of a freeform surface with any continuous shape. The technique produces straight moiré fringes that rotate in a circle regardless of the shape of interference fringes and tested surface shapes. The vortex phase is used to record only one interferogram before the measurement for subsequent data processing, and then it no longer participates in the displacement measurement process. Therefore, this technology can be employed to remold traditional DMIs. Simulations and experiments validating the method are presented.
Quasi-distributed quartz enhanced photoacoustic spectroscopy sensing based on hollow waveguide micropores
Authors: Chen Weipeng , Qiao Shunda , He Ying , Zhu Jie , Wang Kang , Xiao Limin , Ma Yufei
Published: April 2024

In this Letter, a quasi-distributed quartz enhanced photoacoustic spectroscopy (QEPAS) gas sensing system based on hollow waveguide micropores (HWGMP) was reported for the first time, to the best of our knowledge. Three micropores were developed on the HWG to achieve distributed detection units. Three self-designed quartz tuning forks (QTFs) with low resonant frequency of 8.7 kHz were selected as the acoustic wave transducer to improve the detection performance. Compared with micro-nano fiber evanescent wave (FEW) QEPAS, the HWGMP-QEPAS sensor has advantages such as strong anti-interference ability, low loss, and low cost. Acetylene (C2H2) was selected as the target gas to verify the characteristics of the reported sensor. The experimental results showed that the three QTFs almost had the same sensing ability and possessed an excellent linear concentration response to C2H2. The minimum detection limits (MDLs) for the three QTFs were determined as 68.90, 68.31, and 66.62 ppm, respectively. Allan deviation analysis indicated that the system had good long-term stability, and the MDL can be improved below 3 ppm in an average time of 1000 s.
Trident edge coupler on thin-film lithium niobate for optimized coupling of octave-separated wavelengths for nonlinear applications
Authors: Gerguis John O. , Chang Gregory , Qi Minghao
Published: April 2024

We introduce a trident edge coupler design optimized for the simultaneous coupling of two widely separated wavelengths (2 µm and 1 µm) between a lensed fiber and a 600-nm-thick X-cut lithium-niobate-on-insulator (LNOI) waveguide. These wavelengths are commonly encountered in nonlinear wave mixing applications, representing either the fundamental and second harmonics in second harmonic generation (SHG) processes or the leading and trailing edges of an octave-spanning spectrum generated through broadband nonlinear processes such as frequency comb or supercontinuum generation. Achieving efficient coupling between fibers and strongly confined waveguides in integrated platforms, such as LNOI, can be challenging due to the significant difference in spot sizes between the two wavelengths. Our trident edge coupler offers coupling losses below 1.4 dB for the 2 µm and 1 µm spots simultaneously, showcasing an average transmission enhancement of around 10% compared to the baseline of a single linear taper. Furthermore, it enables a reduction of transmission at 1.5 µm, a typical pump wavelength, with an attenuation of transmission over 10 dB compared to those at the 2 µm and 1 µm wavelengths.
Realization of high-performance laser frequency stability in atomic sensor based on self-referencing phase-locked system
Authors: Cao Zhaoyang , Xie Han , Zhou Xinxiu , Shang Jingcheng
Published: April 2024

We conduct a theoretical and experimental analysis for a self-referencing phase-locked module based on the delay-unbalanced Mach-Zehnder interferometer (UMZI) and optical phase-locked loop (OPLL) in a saturated absorption spectrum (SAS) frequency stabilization system. The designed self-referencing phase-locked system achieves significant suppressions of laser phase, frequency noise and modulation noise while keeping a highly stable frequency stabilization in both short-term and long-term. For the short-term performance, we achieve a laser linewidth compression of 3.3 MHz to 2 kHz, the laser phase noise is suppressed from -12.508 dBc/Hz to -95.461 dBc/Hz, and the frequency stability is improved from 2.663x10^-12 to 2.992x10^-13. For the long-term performance, the laser wavelength stability is improved from 3.113x10^-8 to 6.23710^-10. The proposed self-referencing phase-locked system provides a high-performance solution with both short-term and long-term performance of laser for spin-exchange relaxation-free (SERF) atomic sensor.
Optimized Noise Performance in All-PM Linear Mode-Locked Fiber Oscillators through Mitigation of Cross-Phase Modulation
Authors: Edelmann Marvin , hua yi , Shafak Kemal , Sharkawy Yousef , Pergament Mikhail , Kaertner Franz
Published: April 2024

Here, we demonstrate improved noise performance and pulse quality of fiber oscillators mode-locked with all-PM, linear self-stabilized interferometers (LSI) through intra-cavity suppression of cross-phase modulation (XPM) in both soliton and stretched-pulse regime. A modified LSI oscillator setup is constructed, which allows to switch between standard configuration, and a performance-enhanced configuration with XPM suppression via implementation of a highly birefringent intra-cavity crystal. Comparative measurements in soliton and stretched-pulse regime verify not only a drastically improved time-domain output pulse shape and spectral quality, but further a significant suppression of timing-jitter and relative intensity noise (RIN) for the XPM-suppressed laser configuration. In soliton regime, up to ~3.5 dB reduction in integrated timing-jitter (9 kHz - 5 MHz) are verified from 87 fs to 39 fs RMS, and a suppression of integrated RIN (1 Hz - 5 MHz) from 0.08% to 0.06%. Correspondingly, in stretched-pulse regime, the integrated jitter (3 kHz – 5 MHz) is reduced from ~22 fs down to 14.5 fs RMS and the integrated RIN (1 Hz - 5 MHz) from ~0.07% to 0.04%.
Locations and structures of influenza A virus packaging-associated signals and other functional elements via an in silico pipeline for predicting constrained features in RNA viruses
Authors: Beniston Emma , Skittrall Jordan P.
Published: April 2024

Influenza A virus contains regions of its segmented genome associated with ability to package the segments into virions, but many such regions are poorly characterised. We provide detailed predictions of the key locations within these packaging-associated regions, and their structures, by applying a recently-improved pipeline for delineating constrained regions in RNA viruses and applying structural prediction algorithms. We find and characterise other known constrained regions within influenza A genomes, including the region associated with the PA-X frameshift, regions associated with alternative splicing, and constraint around the initiation motif for a truncated PB1 protein, PB1-N92, associated with avian viruses. We further predict the presence of constrained regions that have not previously been described. The extra characterisation our work provides allows investigation of these key regions for drug target potential, and points towards determinants of packaging compatibility between segments.
Neutral competition explains the clonal composition of neural organoids
Authors: Pflug Florian G. , Haendeler Simon , Esk Christopher , Lindenhofer Dominik , Knoblich Jürgen A. , von Haeseler Arndt
Published: April 2024

Neural organoids model the development of the human brain and are an indispensable tool for studying neurodevelopment. Whole-organoid lineage tracing has revealed the number of progenies arising from each initial stem cell to be highly diverse, with lineage sizes ranging from one to more than 20,000 cells. This high variability exceeds what can be explained by existing stochastic models of corticogenesis and indicates the existence of an additional source of stochasticity. To explain this variability, we introduce the SAN model which distinguishes Symmetrically diving, Asymmetrically dividing, and Non-proliferating cells. In the SAN model, the additional source of stochasticity is the survival time of a lineage’s pool of symmetrically dividing cells. These survival times result from neutral competition within the sub-population of all symmetrically dividing cells. We demonstrate that our model explains the experimentally observed variability of lineage sizes and derive the quantitative relationship between survival time and lineage size. We also show that our model implies the existence of a regulatory mechanism which keeps the size of the symmetrically dividing cell population constant. Our results provide quantitative insight into the clonal composition of neural organoids and how it arises. This is relevant for many applications of neural organoids, and similar processes may occur in other developing tissues both in vitro and in vivo.
Collider bias correction for multiple covariates in GWAS using robust multivariable Mendelian randomization
Authors: Wang Peiyao , Lin Zhaotong , Xue Haoran , Pan Wei
Published: April 2024

Genome-wide association studies (GWAS) have identified many genetic loci associated with complex traits and diseases in the past 20 years. Multiple heritable covariates may be added into GWAS regression models to estimate direct effects of genetic variants on a focal trait, or to improve the power by accounting for environmental effects and other sources of trait variations. When one or more covariates are causally affected by both genetic variants and hidden confounders, adjusting for them in GWAS will produce biased estimation of SNP effects, known as collider bias. Several approaches have been developed to correct collider bias through estimating the bias by Mendelian randomization (MR). However, these methods work for only one covariate, some of which utilize MR methods with relatively strong assumptions, both of which may not hold in practice. In this paper, we extend the bias-correction approaches in two aspects: first we derive an analytical expression for the collider bias in the presence of multiple covariates, then we propose estimating the bias using a robust multivariable MR (MVMR) method based on constrained maximum likelihood (called MVMR-cML), allowing the presence of invalid instrumental variables (IVs) and correlated pleiotropy. We also established the estimation consistency and asymptotic normality of the new bias-corrected estimator. We conducted simulations to show that all methods mitigated collider bias under various scenarios. In real data analyses, we applied the methods to two GWAS examples, the first a GWAS of waist-hip ratio with adjustment for only one covariate, body-mass index (BMI), and the second a GWAS of BMI adjusting metabolomic principle components as multiple covariates, illustrating the effectiveness of bias correction.
Development of a non-infectious control for viral hemorrhagic fever PCR assays
Authors: Knox Matthew A. , Bromhead Collette , Hayman David TS
Published: April 2024

Assay validation is an essential component of disease surveillance testing, but can be problematic in settings where access to positive control material is limited and a safety risk for handlers. Here we describe a single non-infectious synthetic control that can help develop and validate the PCR based detection of the viral causes of Crimean-Congo hemorrhagic fever, Ebola virus disease, Lassa fever, Marburg virus disease and Rift Valley fever. We designed non-infectious synthetic DNA oligonucleotide sequences incorporating primer binding sites suitable for five assays, and a T7 promotor site which was used to transcribe the sequence. Transcribed RNA was used as template in a dilution series, extracted and amplified with RT-PCR and RT-qPCR to demonstrate successful recovery and determine limits of detection in a range of laboratory settings. Our results show this approach is adaptable to any diagnostic assay requiring validation of nucleic acid extraction and/or amplification, particularly where sourcing reliable, safe material for positive controls is infeasible.
Live-attenuated CHIKV vaccine with rearranged genome replicates in vitro and induces immune response in mice
Authors: Tretyakova Irina , Joh Joongho , Gearon Mary , Kraenzle Jennifer , Goedeker Sidney , Pignataro Ava , Alejandro Brian , Lukashevich Igor S. , Chung Donghoon , Pushko Peter
Published: April 2024

Chikungunya fever virus (CHIKV) is a mosquito-borne alphavirus that causes wide-spread human infections and epidemics in Asia, Africa and recently, in the Americas. CHIKV is considered a priority pathogen by CEPI and WHO. Despite recent approval of a live-attenuated CHIKV vaccine, development of additional vaccines is warranted due to the worldwide outbreaks of CHIKV. Previously, we developed immunization DNA (iDNA) plasmid capable of launching live-attenuated CHIKV vaccine in vivo. Here we report the use of CHIKV iDNA plasmid to prepare a novel, live-attenuated CHIKV vaccine V5040 with rearranged RNA genome. In V5040, genomic RNA was rearranged to encode capsid gene downstream from the glycoprotein genes. Attenuated mutations derived from experimental CHIKV 181/25 vaccine were also engineered into E2 gene of V5040. The DNA copy of rearranged CHIKV genomic RNA with attenuated mutations was cloned into iDNA plasmid pMG5040 downstream from the CMV promoter. After transfection in vitro, pMG5040 launched replication of V5040 virus with rearranged genome and attenuating E2 mutations. Furthermore, V5040 virus was evaluated in experimental murine models for general safety and immunogenicity. Vaccination with V5040 virus subcutaneously resulted in elicitation of CHIKV-specific, virus-neutralizing antibodies. The results warrant further evaluation of V5040 virus with rearranged genome as a novel live-attenuated vaccine for CHIKV.
Prevalence and factors associated with burnout among health professionals of a public hospital network during the COVID-19 pandemic
Authors: Martins Patricia , Luzia Richardson Warley Siqueira , Filho Jair Alves Pereira , Welsh Kelly Silva , Fuzikawa Cíntia , Nicolato Rodrigo , Alemão Márcia Mascarenhas , Gonçalves Márcio Augusto , Cavalheiro José Carlos , Ávila Ianny Dumont , Veiga Ricardo Teixeira
Published: April 2024

Burnout is most commonly defined as a syndrome characterized by emotional exhaustion, cynicism, and ineffectiveness, which occurs in response to chronic stressors at work. It can adversely affect health workers’ physical and mental health, and the quality of care provided. The COVID-19 pandemic increased stressors and could impact burnout prevalence in this group. There is a lack of information regarding the prevalence of burnout among hospital health workers in Brazil. A newer definition of burnout has been proposed that considers three different clinical profiles: the frenetic, underchallenged and worn-out subtypes. This differentiation could lead to interventions tailored for each subtype. The present study aimed to estimate the prevalence of burnout, its subtypes, and associated factors in workers of a public hospital network in Brazil, during the pandemic. A total of 143 randomly selected participants answered an online form that included sociodemographic and occupational items, and the Burnout Clinical Subtypes Questionnaire, a summarized version. This questionnaire evaluates three burnout dimensions (overload, lack of development, neglect) that can be used to discriminate the three burnout subtypes (frenetic, underchallenged, worn-out, respectively); higher scores indicate higher burnout levels. The prevalence of burnout was high (53.85%), similar to other studies during the pandemic. The most common subtypes were ‘frenetic’ (34.97%), characterized by increased efforts to meet work demands, to the point of neglecting personal needs, and ‘lack of development’ (23.78%), characterized by a sense that work is uninteresting and does not contribute to personal development, and a perfunctory behavior towards tasks. Age was associated with burnout: workers with less than 51 years presented higher levels of burnout. These findings indicate the need for effective interventions to prevent and/or treat burnout. The assessment of burnout subtypes can allow managers to better understand the processes affecting employees, and inform actions to improve workforce health.
Effects of brief mindfulness training on smoking cue-reactivity in tobacco use disorder: Study protocol for a randomized controlled trial
Authors: Cheng Linlin , Luo Miaoling , Ge Jie , Fu Yu , Gan Quan , Chen Zhuangfei
Published: April 2024

Background

The prevalence of Tobacco Use Disorder (TUD) represents a significant and pressing global public health concern, with far-reaching and deleterious consequences for individuals, communities, and healthcare systems. The craving caused by smoking cue is an important trigger for relapse, fundamentally hindering the cessation of cigarette smoking. Mindfulness interventions focusing on cue-reactivity was effective for the treatment of related dependence. Brief mindfulness training (BMT) meets the short-term needs for intervention but the effects still need to be examined. The objective of the present study is to investigate the impact of BMT intervention on smoking cue-reactivity among Chinese college students with TUD, to uncover the dynamic models of brain function involved in this process.

Method

A randomized control trial (RCT) based on electroencephalography (EEG) was designed. We aim to recruit 90 participants and randomly assign to the BMT and control group (CON) with 1:1 ratio. A brief mindfulness training will be administered to experimental group. After the intervention, data collection will be conducted in the follow-up stage with 5 timepoints of assessments. EEG data will be recorded during the smoking cue-reactivity task and ‘STOP’ brief mindfulness task. The primary outcomes include subjective reports of smoking craving, changes in EEG indicators, and mindfulness measures. The secondary outcomes will be daily smoking behaviours, affect and impulsivity, as well as indicators reflecting correlation between mindfulness and smoking cue-reactivity. To evaluate the impact of mindfulness training, a series of linear mixed-effects models will be employed. Specifically, within-group effects will be examined by analysing the longitudinal data. Additionally, the effect size for all statistical measurements will be reported, offering a comprehensive view of the observed effects.

Discussion

The current study aims to assess the impact of brief mindfulness-based intervention on smoking cue-reactivity in TUD. It also expected to enhance our understanding of the underlying processes involved in brain function and explore potential EEG biomarkers at multiple time points.

Trial registration

Trial registration number: ChiCTR2300069363, registered on 14 March 2023. Protocol Version 1.0., 10 April 2023.
Port Harcourt residents’ response to NPC’s campaign against inaccurate and malicious news publications
Authors: Nwanmereni Daniel
Published: April 2024

In its effort to ensure that media contents are not slanted to misinform the public, the Nigerian Press Council (NPC) leaves a window for members of the public to lodge complaints about perceived inaccuracies and malicious publications with the Council for proper investigation and action. Notwithstanding this window, which also offers the public an opportunity to entrench responsible journalism, it appears that many Nigerian citizens do not take advantage of the directive. This study investigated Port Harcourt residents’ response to NPC’s directive against inaccurate and malicious news reports. Among other objectives, the study investigated Port Harcourt residents’ response to the directive. The critical political-economy theory provided theoretical cornerstone to the study. Using the survey research design, a sample size of 384 respondents was drawn from a population of 205,507. Findings of the study showed that many residents of Port Harcourt had observed inaccurate and malicious news reports but failed to report to the NPC due to fear of being victimized. The study recommended, among other measures, that NPC should assure Nigerian citizens that complaints arising from perceived inaccurate news publications would be treated as confidential.