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Temporal interference electrical neurostimulation (TI) is a relatively new method of non-invasive neurostimulation that may be able to stimulate deep brain regions without stimulating the overlying superficial regions. Although some recent studies have demonstrated the success of TI in modulating task-induced BOLD activity in humans, there is limited information on intended and off-target effects of TI during resting-state. We simultaneously performed TI stimulation with the set-up optimized for maximum focality in the left caudate and collected resting-state fMRI data to investigate the effects of TI on human BOLD signals. We found increased BOLD activation in a part of the mid-orbitofrontal cortex (OFC) and parahippocampal gyrus. Results indicate that TI can induce increased BOLD activation in the region that receives the highest magnitude of TI amplitude modulation in humans, with good safety and tolerability profiles. We also show the limits of spatial precision and explore the nature and causes of additional off-target effects. TI may be a promising approach for addressing questions about the causal role of deep brain structures in human cognition and may also afford new clinical treatments.

Background: Multimodal approach of psychotherapy has been found to be effective for managing the excessive use of technology. Yoga, a holistic mind–body therapy, has been observed to be a useful adjuvant in managing substance use disorders. Yoga is also known to reduce stress and enhance overall well-being. The aim of this study was to examine whether yoga as an adjuvant treatment to psychotherapy is better than psychotherapy alone in reducing dysfunction and severity due to excessive technology use. Methods: A two-arm randomized controlled prospective study design was followed with assessor blinding and allocation concealment. Thirty consenting young adults (22 males), scoring above 36 on the Internet Addiction Test, were randomly allocated to either: Group A = psychotherapy + yoga or Group B = psychotherapy alone. Both groups received 8 sessions of psychotherapy in the 1st month. In addition, Group A received additional 10 sessions a specific yoga program (by trained professionals). After that, monthly booster sessions (supervised yoga sessions performed with direct one-on-one contact with the yoga therapist) were organized and post-assessment was conducted at 12 weeks. Each subject was assessed using the Internet Addiction Test-Short Form, Internet Gaming Disorder Scale-Short Form, Smartphone Addiction Scale-Short Version, and Kessler Psychological Distress Scale at baseline and after 12 weeks. Results: As compared to Group B, Group A had significantly reduced Internet use (F = 5.61, P = 0.02, ηp2 = 0.17), smartphone use (F = 4.76, P = 0.03, ηp2 = 0.15), psychological distress (F = 7.71, P = 0.01, ηp2 = 0.22), and weekday use (Z = −2.0, P = 0.05, ηp2 = 0.15) along with enhanced treatment adherence and retention. Conclusion: Yoga as an adjuvant therapy with multimodal psychological intervention for excessive use of technology was found to be effective. This carries clinical implications for mental health professionals.

Objectives: Gross description of gastro-intestinal malignancy is facilitated by endoscopy of the upper and lower gastro-intestinal tract and also provides tissue for definitive diagnosis. Currently, direct vision endoscopic forceps biopsy & FNAC are two standard techniques used to establish a preoperative diagnosis in gastro-intestinal malignancies. The objective of our study is to evaluate the diagnostic accuracy of endoscopic findings when combined with fine needle aspiration and endoscopic biopsy in the diagnosis of gastrointestinal malignancies. So, we compare both techniques (endoscopic forceps biopsy & endoscopic FNAC) to each other and how accurately both techniques are diagnosing the lesion in combination with each other. Material and Method: In our study, 40 cases of suspected gastro-intestinal malignancies underwent endoscopic biopsy & FNAC in a period of one and half years. Result: Out of 40 cases, total malignant lesions were accounting for 32 cases. 27 cases were diagnosed as malignant by biopsy. FNAC showed positive results in 28 cases. The FNAC was found to be 81.82% Sensitive and 85.71% Specific & an accuracy of 82.5%. Biopsy had Sensitivity 81.82% Specificity 100% & Accuracy 85%. The Combined accuracy of both endoscopic FNAC and biopsy was 93.93%. Conclusion: The advent of endoscopic biopsy & FNAC have facilitated the detection & diagnosis of gastrointestinal malignancies. Biopsy though is considered to be diagnostic, Fine Needle Aspiration along with Biopsy can help in the detection of additional cases of malignancy. Thus, both procedures applied together can detect more malignant cases & can establish a more definitive diagnosis. Keywords: Endoscopy, FNAC, Biopsy, Gastrointestinal Malignancies

Background: Mechanical ventilation is essential for managing acute respiratory failure, but traditional methods of assessing oxygenation, like the PaO2/FiO2 ratio, pose challenges due to invasiveness and cost. Objective: This single-centre prospective observational study aimed to assess the potential of the non-invasive Oxygen Saturation Index (OSI), utilising SpO2 measurements, to diagnose hypoxemia in mechanically ventilated adults. The study sought to establish correlations between OSI, oxygenation index (OI), PaO2/FiO2 ratio and SpO2/FiO2 ratio. Methods: From August 2022 to July 2023, data was collected from 1055 mechanically ventilated intensive care unit patients. Statistical analysis included correlation tests, receiver operating curve (ROC) analysis and cut-off value determination for hypoxemia diagnosis. Results: We found that the P/F ratio had a statistically significant negative correlation with OI (correlation coefficient -0.832, P value: 0.000 in hypoxemic group and correlation coefficient -0.888, P value: 0.000 in the non-hypoxemic group), and OSI (correlation coefficient -0.746, P value: 0.000 in hypoxemic group and correlation coefficient -0.629, P value: 0.000 in non-hypoxemic group) and has a positive correlation with P/F ratio (correlation coefficient 0.92, P value: 0.000 in hypoxemic group and correlation coefficient -0.67, P value: 0.000 in non-hypoxemic group). OI and OSI had a statistically significant correlation (correlation coefficient 0.955, P value: 0.000 in hypoxemic group and correlation coefficient 0.815, P value: 0.000 in non-hypoxemic group). on ROC analysis P/F ratio was the most accurate in predicting hypoxia followed by OI and OSI. with a cut-off value, of OI being 7.07, and that for OSI being 3.90, at an 80% sensitivity level to diagnose hypoxemia. Conclusion: OSI can serve as a dependable surrogate for OI, simplifying ARDS severity assessment. The P/F ratio is the most accurate predictor of hypoxia. Further research, especially in larger multicentre studies, is needed to validate these findings and explore the long-term clinical implications of using OSI for oxygenation monitoring in mechanically ventilated patients.

Objective To compare health-related quality of life (HRQOL) in patients undergoing radical cystectomy with ileal conduit (RC) or bladder preservation (BP) with (chemo)radiotherapy for bladder cancer.Methods and analysis Patients with bladder cancer, stage cT1–T4, cN0–N1, M0 with a minimum follow-up of 6 months from curative treatment (RC or BP) and without disease were eligible for inclusion. Two HRQOL instruments were administered: Bladder Cancer Index (BCI) for bladder cancer-specific HRQOL and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). The mean QOL scores across various domains and specific questions were compared between the two treatment groups using an independent t-test.Results Out of the 104 enrolled patients, 56 underwent RC and 48 opted for BP, with 95 (91.3%) being male. The median time from treatment completion to QOL assessment was 22 months (IQR 10–56). The median age for the entire cohort was 62 years (IQR 55–68), 65.5 years (IQR 55–71) in BP and 59.5 years (IQR 55–66) in RC. There was no significant difference in mean BCI urinary and bowel scores in function or bother subdomains between the two groups. Overall, BCI sexual scores were low in both groups but significantly better after BP (BPmean 56.9, RCmean 41.5, p=0.01). Mean scores for sexual function subdomain were BPmean 38.4 and RCmean 25 (p=0.07) and for sexual bother were BPmean 81 RCmean 62 (p=0.02). The EORTC QLQ-C30 outcomes did not show a significant difference in either group.Conclusion The BP group showed significantly better results in the sexual domain compared with the RC group. Both groups had good QOL in terms of urinary and bowel functions

Viruses have been responsible for many epidemics and pandemics that have impacted human life globally. The COVID-19 pandemic highlighted both our vulnerability to viral outbreaks, as well as the mobilization of the scientific community to come together to combat the unprecedented threat to humanity. Cryo-electron microscopy (cryo-EM) played a central role in our understanding of SARS-CoV-2 during the pandemic and continues to inform about this evolving pathogen. Cryo-EM with its two popular imaging modalities, single particle analysis (SPA) and cryo-electron tomography (cryo-ET), has contributed immensely to understanding the structure of viruses and interactions that define their life cycles and pathogenicity. Here, we review how cryo-EM has informed our understanding of three distinct viruses, of which two - HIV-1 and SARS-CoV-2 infect humans, and the third, bacteriophages, infect bacteria. For HIV-1 and SARS-CoV-2 our focus is on the surface glycoproteins that are responsible for mediating host receptor binding, and host and cell membrane fusion, while for bacteriophages, we review their structure, capsid maturation, attachment to the bacterial cell surface and infection initiation mechanism.

Learning requires the ability to link actions to outcomes. How motivation facilitates learning is not well understood. We designed a behavioral task in which mice self-initiate trials to learn cue-reward contingencies and found that the anterior cingulate region of the prefrontal cortex (ACC) contains motivation-related signals to maximize rewards. In particular, we found that ACC neural activity was consistently tied to trial initiations where mice seek to leave unrewarded cues to reach reward-associated cues. Notably, this neural signal persisted over consecutive unrewarded cues until reward-associated cues were reached, and was required for learning. To determine how ACC inherits this motivational signal we performed projection-specific photometry recordings from several inputs to ACC during learning. In doing so, we identified a ramp in bulk neural activity in orbitofrontal cortex (OFC)-to-ACC projections as mice received unrewarded cues, which continued ramping across consecutive unrewarded cues, and finally peaked upon reaching a reward-associated cue, thus maintaining an extended motivational state. Cellular resolution imaging of OFC confirmed these neural correlates of motivation, and further delineated separate ensembles of neurons that sequentially tiled the ramp. Together, these results identify a mechanism by which OFC maps out task structure to convey an extended motivational state to ACC to facilitate goal-directed learning.

Purpose: To study the visual outcomes and patient satisfaction profile among patients post phacoemulsification with the Vivity intraocular lens (IOL) implantation. Method: This was a hospital-based, prospective, observational study cons isting of 64 study subjects who were followed up for 1 month to look for the objective and subjective aspects of visual outcomes of Vivity IOLs. Objective parameters included distance vision, intermediate vision, near vision, and contrast-sensitivity, whereas subjective parameters were assessed using the modified Catquest 9SF Questionnaire. Results: Among the total study population, 82.5% were males and 17.5% were females, the most common age group was 41–50 years. In addition, 93.6% had a distance visual acuity of 6/9 or better, 93.7% had an intermediate vision of N18 or better, whereas 50.8% had a near vision of N18 or better. Good contrast sensitivity was reported among 79.4% of subjects, and 95.2% of study subjects were comfortable with distance vision, whereas 74.6% and 22.2% were comfortable with intermediate and near vision, respectively. Only two patients complained of glare, whereas none complained of halos and starbursts. A total of 88.8% of study subjects were satisfied with their postoperative visual outcomes, whereas 87.3% were willing to Vivity IOL in the other eye or were willing to refer this IOL to others. Conclusion: The study demonstrated a good distance and intermediate visual acuity post-Vivity IOL implantation, whereas near activities mostly required the use of near-addition glasses, though requiring lesser near-addition power.

The occupation fraction of massive black holes (MBHs) in low mass galaxies offers interesting insights into initial black hole seeding mechanisms and their mass assembly history, though disentangling these two effects remains challenging. Using the {\sc Romulus} cosmological simulations we examine the impact of environment on the occupation fraction of MBHs in low mass galaxies. Unlike most modern cosmological simulations, {\sc Romulus} seeds MBHs based on local gas properties, selecting dense (n>3 cm^-3, 15 times the threshold for star formation), pristine (Z3), a difference arises as late-forming dwarfs -- which do not exist in the cluster environment -- begin to dominate in the field and pull the MBH occupation fraction down for low mass galaxies. Additionally, prior to in-fall some cluster dwarfs are similar to progenitors of massive, isolated galaxies, indicating that they might have grown to higher masses had they not been impeded by the cluster environment. While the population of MBHs in dwarf galaxies is already widely understood to be important for understanding MBH formation, this work demonstrates that environmental dependence is important to consider as future observations search for low mass black holes in dwarf galaxies.

Analytical hierarchy process (AHP) typically involves pairwise comparisons to establish the relative importance of criteria and alternatives. This study can verify these comparisons through consistency checks to ensure that respondents provide reliable and consistent judgments. The proposed model is implemented to evaluate the optimum route alignment between two locations, for the outer area of Allahabad City, India. The optimal route obtained is the path with minimum cost in the alignment decision and it meets all the factors related to environmental, technical, social, and economic criteria. Four alternative route alignments arise. Based on multi-criteria evaluation, four alignments are compared and one of the optimal route alignments is selected. A multi-criteria evaluation is performed to compare the four routes’ alignment using AHP and surface cost analysis. The technical route alignment with the highest priority index of 0.297956 with a minimum cost of 4,619 units is finally considered as optimum route alignment.

Pharmacophores such as hydroxyethylamine (HEA) and phthalimide (PHT) have been identified as potential synthons for the development of compounds against various parasitic infections. In order to further advance our progress, we conducted an experiment utilising a collection of PHT and HEA derivatives through phenotypic screening against a diverse set of protist parasites. This approach led to the identification of a number of compounds that exhibited significant effects on the survival of Entamoeba histolytica, Trypanosoma brucei, and multiple life-cycle stages of Leishmania spp. The Leishmania hits were pursued due to the pressing necessity to expand our repertoire of reliable, cost-effective, and efficient medications for the treatment of leishmaniases. Antileishmanials must possess the essential capability to efficiently penetrate the host cells and their compartments in the disease context, to effectively eliminate the intracellular parasite. Hence, we performed a study to assess the effectiveness of eradicating L. infantum intracellular amastigotes in a model of macrophage infection. Among eleven L. infantum growth inhibitors with low-micromolar potency, PHT-39, which carries a trifluoromethyl substitution, demonstrated the highest efficacy in the intramacrophage assay, with an EC50 of 1.2 +/- 3.2 μM. Cytotoxicity testing of PHT-39 in HepG2 cells indicated a promising selectivity of over 90-fold. A chemogenomic profiling approach was conducted using an orthology-based method to elucidate the mode of action of PHT-39. This genome-wide RNA interference library of T. brucei identified sensitivity determinants for PHT-39, which included a P-type ATPase that is crucial for the uptake of miltefosine and amphotericin, strongly indicating a shared route for cellular entry. Notwithstanding the favourable properties and demonstrated efficacy in the Plasmodium berghei infection model, PHT-39 was unable to eradicate L. major infection in a murine infection model of cutaneous leishmaniasis. Currently, PHT-39 is undergoing derivatization to optimize its pharmacological characteristics.

In the past decade, stereotactic body radiation therapy (SBRT) has emerged as a valid treatment option for patients with localized prostate cancer. Despite the promising results of ultra-hypofractionation in terms of tolerance and disease control, the toxicity profile of SBRT for prostate cancer patients with a history of surgical treatment of benign prostate hyperplasia is still underreported. Here we present an overview of the available data on urinary morbidity for prostate cancer patients treated with SBRT after prior surgical treatments for benign prostate hyperplasia. Technical improvements useful to minimize toxicity and possible treatments for radiation-induced urethritis are discussed.

ABSTRACTFungal endophytes have emerged as a promising source of secondary metabolites with significant potential for various applications in the field of biomedicine. The biosynthetic gene clusters of endophytic fungi are responsible for encoding several enzymes and transcriptional factors that are involved in the biosynthesis of secondary metabolites. The investigation of fungal metabolic potential at genetic level faces certain challenges, including the synthesis of appropriate amounts of chemicals, and loss of the ability of fungal endophytes to produce secondary metabolites in an artificial culture medium. Therefore, there is a need to delve deeper into the field of fungal genomics and transcriptomics to explore the potential of fungal endophytes in generating secondary metabolites governed by biosynthetic gene clusters. The silent biosynthetic gene clusters can be activated by modulating the chromatin structure using chemical compounds. Epigenetic modification plays a significant role by inducing cryptic gene responsible for the production of secondary metabolites using DNA methyl transferase and histone deacetylase. CRISPR-Cas9-based genome editing emerges an effective tool to enhance the production of desired metabolites by modulating gene expression. This review primarily focuses on the significance of epigenetic elicitors and their capacity to boost the production of secondary metabolites from endophytes. This article holds the potential to rejuvenate the drug discovery pipeline by introducing new chemical compounds.

Abstract Background Recent years have seen record levels of migration to Europe. Female migrants are at heightened risk of developing mental health disorders, yet they face barriers to accessing mental health services in their host countries. This systematic review aims to summarise the barriers and facilitators to accessing mental health support for female migrants in Europe. Methods The review follows PRISMA guidelines, and the protocol was pre-published on PROSPERO. Six electronic databases were searched: CINAHL, Global Health Database, Medline, PsycARTICLES, PsycINFO and Web of Science. Thematic analysis was undertaken on the identified studies. A feminist quality appraisal tool was applied. Results Eight qualitative, six quantitative and five mixed methods studies were identified. Barriers included a lack of information, stigma, religious and cultural practices and beliefs, and a lack of consideration of gender-specific needs within the health system. Gender-sensitive services, supportive general practitioners and religious leaders facilitated access. Conclusions The design of mental health research, services, policies, and commissioning of support for migrants must consider female migrant needs. Mental health support services must be culturally aware and gender sensitive. Registration The review protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO, registration number CRD42021235571.

[This corrects the article DOI: 10.1371/journal.pone.0264673.].

Background The proposed research aims to test the effects and mechanisms of a six-month yoga-based intervention as an add-on to standard treatment in opioid use disorder (OUD) by conducting a randomized controlled study with the following primary outcome variables: 1) clinical: abstinence (opioid negative urine test), and reductions in pain and craving, and 2) mechanisms: reward circuit activation in response to opioid visual cue craving paradigm, activation in response to a cognitive control task, and resting state functional connectivity through fMRI, and plasma beta-endorphin levels. Secondary outcome variables are perceived stress, anxiety, sleep quality, cognitive performance, pain threshold, buprenorphine dosage and side effects, withdrawal symptoms, socio-occupational functioning, vedic personality traits, heart rate variability, serum cortisol, and brain GABA levels through magnetic resonance spectroscopy (MRS). Methods In this single-blinded, randomized, controlled, parallel-group superiority trial with 1:1 allocation ratio, 164 patients with OUD availing the outpatient/ inpatient clinical services at a tertiary mental healthcare hospital in India will be enrolled after giving informed consent. Consecutive consenting patients will be randomly allotted to one of the two groups – yoga arm (standard treatment + yoga-based intervention), or waitlist group (standard treatment alone). Allocation concealment will be followed, the clinicians, outcome assessors and data analysts will remain blind to subject-group allocation. A validated and standardized yoga program for OUD will be used as an intervention. Participants in the yoga arm will receive 10 supervised in-person sessions of yoga in the initial two weeks followed by tele-yoga sessions thrice a week for the next 22 weeks. The wait-list control group will continue the standard treatment alone for 24 weeks. Assessments will be done at baseline, two weeks, 12 weeks, and 24 weeks. Data from all randomized subjects will be analysed using intent-to-treat analysis and mixed model multivariate analysis. Dissemination Findings will be disseminated through peer-reviewed publication, conference presentations, and social media. Trial registration number The trial has been registered under Clinical Trials Registry-India with registration number CTRI/2023/03/050737.

The discovery of Little Red Dots (LRDs)—a population of compact, high-redshift, dust-reddened galaxies—is one of the most surprising results from JWST. However, the nature of LRDs is still debated: does the near-infrared emission originate from accreting supermassive black holes (SMBHs), or intense star formation? In this work, we utilize ultra-deep Chandra observations and study LRDs residing behind the lensing galaxy cluster, A2744. We probe the X-ray emission from individual galaxies but find that they remain undetected and provide SMBH mass upper limits of ≲(1.5–16) × 10 ^6 M _⊙ assuming Eddington limited accretion. To increase the signal-to-noise ratios, we conduct a stacking analysis of the full sample with a total lensed exposure time of ≈87 Ms. We also bin the galaxies based on their stellar mass, lensing magnification, and detected broad-line H α emission. For the LRDs exhibiting broad-line H α emission, there is a hint of a stacked signal (∼2.6 σ ), corresponding to an SMBH mass of ∼3.2 × 10 ^6 M _⊙ . Assuming unobscured, Eddington-limited accretion, this black hole (BH) mass is at least 1.5 orders of magnitude lower than that inferred from virial mass estimates using JWST spectra. Given galaxy-dominated stellar mass estimates, our results imply that LRDs do not host overmassive SMBHs and/or accrete at a few percent of their Eddington limit. However, alternative stellar mass estimates may still support that LRDs host overmassive BHs. The significant discrepancy between the JWST and Chandra data hints that the scaling relations used to infer the SMBH mass from the H α line and virial relations may not be applicable for high-redshift LRDs.

The first-generation metal-free stars, referred to as Population III (Pop III) stars, are believed to be the first objects to form out of the pristine gas in the very early Universe. Pop III stars have different structures from the current generation of stars and are important for generating heavy elements and shaping subsequent star formation. However, it is very challenging to directly detect Pop III stars given their high redshifts and short lifetimes. In this Letter, we propose a novel method for detecting Pop III stars through their tidal disruption events (TDEs) by massive black holes. We model the emission properties and calculate the expected rates for these unique TDEs in the early Universe at z ∼ 10. We find that Pop III star TDEs have much higher mass fallback rates and longer evolution timescales compared to solar-type star TDEs in the local Universe, which enhances the feasibility of their detection, although a good survey strategy will be needed for categorizing these sources as transients. We further demonstrate that a large fraction of the flare emissions are redshifted to infrared wavelengths, which can be detected by the JWST and the Nancy Grace Roman Space Telescope (Roman). Last but not least, we find a promising Pop III star TDE detection rate of up to a few tens per year using Roman, based on our current understanding of the black hole mass function in the early Universe.

We report for the first time a sample of 12 supermassive black holes (SMBHs) hosted by low-mass galaxies at cosmic noon, i.e., in a redshift range consistent with the peak of star formation history: z ∼ 1–3. These black holes are 2 orders of magnitude too massive for the stellar content of their hosts when compared with the local relation for active galaxies. These overmassive systems at cosmic noon share similar properties with the high- z sources found ubiquitously in recent James Webb Space Telescope (JWST) surveys (same range of black-hole-to-stellar-mass ratio, bolometric luminosity, and Eddington ratio). We argue that black hole feedback processes, for which there is possible evidence in five of the sources, and the differing environments in galactic nuclei at these respective epochs play a key role in these overmassive systems. These findings contribute to our understanding of the growth and coevolution of SMBHs and their host galaxies across cosmic time, offering a link between the early Universe ( z > 4) observed by JWST and observations of the present-day Universe ( z ≲ 1).

While supermassive black holes (SMBHs) are widely observed in the nearby and distant Universe, their origin remains debated with two viable formation scenarios with light and heavy seeds. In the light seeding model, the seed of the first SMBHs form from the collapse of massive stars with masses of 10–100 M _⊙ , while the heavy seeding model posits the formation of 10 ^4–5 M _⊙ seeds from direct collapse. The detection of SMBHs at redshifts z ≳ 10, edging closer to their formation epoch, provides critical observational discrimination between these scenarios. Here, we focus on the JWST-detected galaxy, GHZ 9, at z ≈ 10 that is lensed by the foreground cluster, A2744. Based on 2.1 Ms deep Chandra observations, we detect a candidate X-ray active galactic nucleus (AGN), which is spatially coincident with the high-redshift galaxy, GHZ 9. The SMBH candidate is inferred to have a bolometric luminosity of $({1.0}_{-0.4}^{+0.5})\times {10}^{46}\ \mathrm{erg}\,{{\rm{s}}}^{-1}$ , which corresponds to a black hole (BH) mass of $({8.0}_{-3.2}^{+3.7})\times {10}^{7}\ {M}_{\odot }$ assuming Eddington-limited accretion. This extreme mass at such an early cosmic epoch suggests the heavy seed origin for this BH candidate. Based on the Chandra and JWST discoveries of extremely high-redshift quasars, we have constructed the first simple AGN luminosity function extending to z ≈ 10. Comparison of this luminosity function with theoretical models indicates an overabundant z ≈ 10 SMBH population, consistent with a higher-than-expected seed formation efficiency.

We present the Next Generation Deep Extragalactic Exploratory Public (NGDEEP) Survey, a deep slitless spectroscopic and imaging Cycle 1 JWST treasury survey designed to constrain feedback mechanisms in low-mass galaxies across cosmic time. NGDEEP targets the Hubble Ultra Deep Field (HUDF) with NIRISS slitless spectroscopy ( ${f}_{\mathrm{lim},\mathrm{line},5\sigma }\approx 1.2\,\times \,$ 10 ^−18 erg s ^−1 cm ^−2 ) to measure metallicities and star formation rates (SFRs) for low-mass galaxies through the peak of the cosmic SFR density (0.5 < z < 4). In parallel, NGDEEP targets the HUDF-Par2 parallel field with NIRCam ( ${m}_{\mathrm{lim},5\sigma }=30.6-30.9$ ) to discover galaxies to z > 12, constraining the slope of the faint end of the rest-ultraviolet luminosity function. NGDEEP overlaps with the deepest HST Advanced Camera for Surveys optical imaging in the sky, F435W in the HUDF ( ${m}_{\mathrm{lim},{\rm{F}}435{\rm{W}}}=29.6$ ) and F814W in HUDF-Par2 ( ${m}_{\mathrm{lim},{\rm{F}}814{\rm{W}}}=30$ ), making this a premier HST+JWST deep field. As a treasury survey, NGDEEP data are public immediately, and we will rapidly release data products and catalogs in the spirit of previous deep-field initiatives. In this paper we present the NGDEEP survey design, summarize the science goals, and detail plans for the public release of NGDEEP reduced data products.

Recently we found compelling evidence for a gravitational-wave background with Hellings and Downs (HD) correlations in our 15 yr data set. These correlations describe gravitational waves as predicted by general relativity, which has two transverse polarization modes. However, more general metric theories of gravity can have additional polarization modes, which produce different interpulsar correlations. In this work, we search the NANOGrav 15 yr data set for evidence of a gravitational-wave background with quadrupolar HD and scalar-transverse (ST) correlations. We find that HD correlations are the best fit to the data and no significant evidence in favor of ST correlations. While Bayes factors show strong evidence for a correlated signal, the data does not strongly prefer either correlation signature, with Bayes factors ∼2 when comparing HD to ST correlations, and ∼1 for HD plus ST correlations to HD correlations alone. However, when modeled alongside HD correlations, the amplitude and spectral index posteriors for ST correlations are uninformative, with the HD process accounting for the vast majority of the total signal. Using the optimal statistic, a frequentist technique that focuses on the pulsar-pair cross-correlations, we find median signal-to-noise ratios of 5.0 for HD and 4.6 for ST correlations when fit for separately, and median signal-to-noise ratios of 3.5 for HD and 3.0 for ST correlations when fit for simultaneously. While the signal-to-noise ratios for each of the correlations are comparable, the estimated amplitude and spectral index for HD are a significantly better fit to the total signal, in agreement with our Bayesian analysis.

Summary: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern, first identified in November 2021, rapidly spread worldwide and diversified into several subvariants. The Omicron spike (S) protein accumulated an unprecedented number of sequence changes relative to previous variants. In this review, we discuss how Omicron S protein structural features modulate host cell receptor binding, virus entry, and immune evasion and highlight how these structural features differentiate Omicron from previous variants. We also examine how key structural properties track across the still-evolving Omicron subvariants and the importance of continuing surveillance of the S protein sequence evolution over time.

Recent years have seen the emergence of moiré materials as an attractive platform for observing a host of novel correlated and topological phenomena. Moiré heterostructures are generated when layers of van der Waals materials are stacked such that consecutive layers are slightly mismatched in their lattice orientation or unit cell size. This slight lattice mismatch gives rise to a long-wavelength moiré pattern that modulates the electronic structure and leads to novel physics. The moiré superlattice results in flat superlattice bands, electron–electron interactions and non-trivial topology that have led to the observation of superconductivity, the quantum anomalous Hall effect and orbital magnetization, among other interesting properties. This review focuses on the experimental observation and theoretical analysis of orbital magnetism in moiré materials. These systems are novel in their ability to host magnetism that is dominated by the orbital magnetic moment of Bloch electrons. This orbital magnetic moment is easily tunable using external electric fields and carrier concentration since it originates in the quantum anomalous Hall effect. As a result, the orbital magnetism found in moiré superlattices can be highly attractive for a wide array of applications including spintronics, ultra-low-power magnetic memories, spin-based neuromorphic computing and quantum information technology.

Abstract The rapid proliferation of smokeless tobacco (SLT) in India has occurred without adequate information on the possible dangers and toxicity of these products. Tobacco flavors as well as nicotine (both protonated and un-protonated) are responsible for health dangers and addiction. The study aimed to offer information on the physical characteristics of commonly used smokeless tobacco products (including microscopic analysis), along with nicotine content (both total and un-protonated), pH, moisture, and flavors. The Standard Operating Procedures (SOPs) validated by the World Health Organization (WHO) recognized Tobacco Testing Laboratory TobLabNet) were applied for the analysis of various constituents of the SLTs. The microscopic analysis indicated that some of the SLT products like khaini were finely processed and available in filter pouches for users’ convenience and prolonged use leading to prolonged retention and addiction potential. Nicotine absorption and availability (both protonated and un-protonated) are affected by moisture and pH. Essences provide a pleasant aroma and flavor, with an increased risk of misuse and other health problems. Few chewing tobacco and Zarda had the lowest levels of un-protonated nicotine (0.10–0.52% and 0.15–0.21%, respectively), whereas Gul, Gudhaku, and Khaini had the highest levels, ranging from 95.33 to 99.12%. Moisture and pH ranged from 4.54 to 50.19% and 5.25–10.07 respectively. Menthol (630.74–9681.42 µg/g) was the most popular flavour, followed by Eucalyptol (118.16–247.77 µg/g) and camphor (148.67 and 219.317 µg/g). SLT’s health concerns and addiction dangers are exacerbated by the high proportion of bioavailable nicotine coupled with flavors. The findings of this study have important implications for the regulation and use of SLT in countries where use of SLT is prevalent.

Abstract Background To assess urinary symptoms and urine cytology as screening tools for cystoscopic detection of local recurrence after bladder‐preserving trimodality treatment (TMT). Methods Patients with muscle‐invasive bladder cancer receiving definitive TMT follow‐up three monthly for 2 years, six monthly for the next 3 years and then yearly, with a clinical review, urine cytology and cystoscopy at each visit (triple assessment, TA). Grade 2+ cystitis/haematuria absent/present was scored 0/1, and urine cytology reported negative/suspicious or positive was scored 0/1, respectively. The performance of these two parameters for predicting local recurrence in cystoscopic biopsy was tested. Other hypothetical surveillance schedules included cystoscopy on alternate visits (COAV), or suspected recurrence (COSR), six‐monthly COSR and six‐monthly TA. Results A total of 630 follow‐up visits in 112 patients with 19 recurrences (7 muscle invasive, 12 non‐muscle invasive) at a median follow‐up of 19 months were analysed. The sensitivity and specificity of clinical symptoms were 47.4% and 92%, and for urine cytology 58% and 85%, respectively. The combination of clinical symptoms and cytology (COSR) was 95% sensitive and 78% specific for local recurrence but 100% sensitive for muscle‐invasive recurrence. Both COAV and COSV schedules showed a high area under the curve (AUC) for detecting local recurrence (COAV = 0.84, COSR = 0.83), muscle‐invasive recurrence (AUC = 0.848 each) and non‐muscle‐invasive recurrence (COAV = 0.82, COSR = 0.81); reducing the need for TAs by 64% and 67% respectively, and overall cost by 18% and 33%, respectively. Conclusion Cystoscopy at suspected recurrence during follow‐up is safe and the most cost‐effective for detecting muscle‐invasive local recurrences, while cystoscopy at alternate visits may be more optimal for detecting any local recurrence.

Objective: Histoplasmosis is a systemic, deep mycotic infection caused by Histoplasma capsulatum. Disseminated histoplasmosis (DH) is synonymous with HIV seropositive immunocompromised individuals; however, isolated histoplasmosis involving the head and neck mucosal sites mimicking malignancy is a clinical predicament. The result, in a superficial biopsy with marked pseudoepitheliomatous hyperplasia (PEH), in a tertiary care cancer center where the number of squamous carcinomas far outnumber the infectious diseases, could be catastrophic. Material and Method: The archives of a tertiary care cancer hospital were searched (2010-2019) for cases of histoplasmosis involving the head and neck mucosal sites in HIV non-reactive patients. Results: Six cases of isolated head and neck histoplasmosis were seen in biopsies from 4 men and 2 women, with an age range of 46-72 years. Three of these patients suffered from chronic illnesses. The most common site involved was the larynx (vocal cords) in three cases, two cases were involving lips, and one involving the tongue. The biopsies were reviewed in-house with a clinical diagnoses of malignancy in all and an outside biopsy diagnosis of "squamous cell carcinoma" in 2 cases. The important histological findings in the biopsy were PEH (3 cases), granulomas (2 cases), lymphoplasmacytic inflammation (all cases). Eosinophils were conspicuous by their absence. Intracellular histoplasma was seen in all cases, albeit to varying density, which was confirmed with GMS stain. Conclusion: A high index of suspicion, meticulous history taking by oncologists, and appropriate distinction of PEH from neoplastic squamous proliferation by pathologists in superficial biopsies and an apropos deeper wedge biopsy are essential to clinch the correct diagnosis.

Abstract Antibody affinity maturation enables adaptive immune responses to a wide range of pathogens. In some individuals broadly neutralizing antibodies develop to recognize rapidly mutating pathogens with extensive sequence diversity. Vaccine design for pathogens such as HIV-1 and influenza has therefore focused on recapitulating the natural affinity maturation process. Here, we determine structures of antibodies in complex with HIV-1 Envelope for all observed members and ancestral states of the broadly neutralizing HIV-1 V3-glycan targeting DH270 antibody clonal B cell lineage. These structures track the development of neutralization breadth from the unmutated common ancestor and define affinity maturation at high spatial resolution. By elucidating contacts mediated by key mutations at different stages of antibody development we identified sites on the epitope-paratope interface that are the focus of affinity optimization. Thus, our results identify bottlenecks on the path to natural affinity maturation and reveal solutions for these that will inform immunogen design aimed at eliciting a broadly neutralizing immune response by vaccination.

We study the black hole mass–host galaxy stellar mass relation, M _BH – M _* , of a sample of z < 4 optically variable active galactic nuclei (AGNs) in the COSMOS field. The parent sample of 491 COSMOS AGNs were identified by optical variability from the Hyper Suprime-Cam Subaru Strategic Program (HSC-SSP) program. Using publicly available catalogs and spectra, we consolidate their spectroscopic redshifts and estimate virial black hole masses using broad-line widths and luminosities. We show that variability searches with deep, high-precision photometry like the HSC-SSP can identity AGNs in low-mass galaxies up to z ∼ 1. However, their black holes are more massive given their host galaxy stellar masses than predicted by the local relation for active galaxies. We report that z ∼ 0.5–4 variability-selected AGNs are meanwhile more consistent with the M _BH – M _* relation for local inactive early-type galaxies. This result is in agreement with most previous studies of the M _BH – M _* relation at similar redshifts and indicates that AGNs selected from variability are not intrinsically different from the broad-line Type 1 AGN population at similar luminosities. Our results demonstrate the need for robust black hole and stellar mass estimates for intermediate-mass black hole candidates in low-mass galaxies at similar redshifts to anchor this scaling relation. Assuming that these results do not reflect a selection bias, they appear to be consistent with self-regulated feedback models wherein the central black hole and stars in galaxies grow in tandem.

Strong gravitational lensing offers a powerful probe of the detailed distribution of matter in lenses, while magnifying and bringing faint background sources into view. Observed strong lensing by massive galaxy clusters, which are often in complex dynamical states, has also been used to map their dark matter (DM) substructures on smaller scales. Deep high-resolution imaging has revealed the presence of strong lensing events associated with these substructures, namely galaxy-scale sub-halos. However, an inventory of these observed galaxy–galaxy strong lensing (GGSL) events is noted to be discrepant with state-of-the-art ΛCDM simulations. Cluster sub-halos appear to be over-concentrated compared to their simulated counterparts yielding an order-of-magnitude higher value of GGSL. In this paper, we explore the possibility of resolving this observed discrepancy by redistributing the mass within observed cluster sub-halos in ways that are consistent within the ΛCDM paradigm of structure formation. Lensing mass reconstructions from data provide constraints on the mass enclosed within apertures and are agnostic to the detailed mass profile within them. Therefore, as the detailed density profile within cluster sub-halos currently remains unconstrained by data, we are afforded the freedom to redistribute the enclosed mass. We investigate if rearranging the mass to a more centrally concentrated density profile helps alleviate the GGSL discrepancy. We report that refitting cluster sub-halos to the ubiquitous ΛCDM-motivated Navarro–Frenk–White profile, and further modifying them to include significant baryonic components, does not resolve this tension. A resolution to this persisting GGSL discrepancy may require more careful exploration of alternative DM models.

The Next Generation Deep Extragalactic Exploratory Public (NGDEEP) survey program was designed specifically to include Near Infrared Slitless Spectroscopic observations (NGDEEP-NISS) to detect multiple emission lines in as many galaxies as possible and across a wide redshift range using the Near Infrared Imager and Slitless Spectrograph. We present early results obtained from the first set of observations (Epoch 1, 50% of the allocated orbits) of this program (NGDEEP-NISS1). Using a set of independently developed calibration files designed to deal with a complex combination of overlapping spectra, multiple position angles, and multiple cross filters and grisms, in conjunction with a robust and proven algorithm for quantifying contamination from overlapping dispersed spectra, NGDEEP-NISS1 has achieved a 3 σ sensitivity limit of 2 × 10 ^−18 erg s ^−1 cm ^−2 . We demonstrate the power of deep wide field slitless spectroscopy (WFSS) to characterize the star formation rates, and metallicity ([O iii ]/H β ), and dust content, of galaxies at 1 < z < 3.5. The latter showing intriguing initial results on the applicability and assumptions made regarding the use of Case B recombination. Further, we identify the presence of active galactic nuclei and infer the mass of their supermassive black holes using broadened restframe Mg ii and H β emission lines. The spectroscopic results are then compared with the physical properties of galaxies extrapolated from fitting spectral energy distribution models to photometry alone. The results clearly demonstrate the unique power and efficiency of WFSS at near-infrared wavelengths over other methods to determine the properties of galaxies across a broad range of redshifts.

Henipaviruses are a genus of emerging pathogens that includes the highly virulent Nipah and Hendra viruses that cause reoccurring outbreaks of disease. Henipaviruses rely on two surface glycoproteins, known as the attachment and fusion proteins, to facilitate entry into host cells. As new and divergent members of the genus have been discovered and structurally characterized, key differences and similarities have been noted. This review surveys the available structural information on Henipavirus glycoproteins, complementing this with information from related biophysical and structural studies of the broader Paramyxoviridae family of which Henipaviruses are members. The process of viral entry is a primary focus for vaccine and drug development, and this review aims to identify critical knowledge gaps in our understanding of the mechanisms that drive Henipavirus fusion.

The YAP protein is a critical oncogenic mediator within the Hippo signaling pathway and has been implicated in various cancer types. In breast cancer, it frequently becomes activated, thereby contributing to developing drug-resistance mechanisms. Recent studies have underscored the intricate interplay between YAP and ferroptosis within the breast tumor microenvironment. YAP exerts a negative regulatory effect on ferroptosis, promoting cancer cell survival and drug resistance. This review offers a concise summary of the current understanding surrounding the interplay between the YAP pathway, ferroptosis, and drug-resistance mechanisms in both bulk tumor cells and cancer stem cells. We also explore the potential of natural compounds alone or in combination with anticancer therapies for targeting the YAP pathway in treating drug-resistant breast cancer. This approach holds the promise of enhancing the effectiveness of current treatments and paving the way for developing novel therapeutics.

Background: Internet addiction is found to be a growing global problem and India is not exceptional. Adolescents are more over addicted to internet and suffering with mental confusions and deviation in behaviour. Several instruments have been developed for assessment of Internet addiction. Internet Addiction Test (IAT) is the most widely used tool to assess internet addiction, but psychometric properties of the IAT have not yet been examined in the Indian adolescence. The aim was to examine the validity and reliability of the 20-item Internet Addiction Test in Indian School Students. Methodology: Seven hundred fifty-two students from a CBSE school of Raipur, India was randomly selected in our study. The reliability and validity of IAT was examined. Confirmatory factor analysis was used to examine the structural validity of IAT. Results: It was found that the factor loading of the IAT varied between 0.40 and 0.82. Cronbach’s alpha coefficient for the scale was found to be 905. The total correlations were calculated and had a value range from 0.406 to 0.659 for the 20 items. The psychometric properties indicate that the factor loading reveal that the test revolve around six factors (Salience, Excessive Use, Neglected Work, Anticipation, Lack of Control, and Neglected Social Life). The Cronbach’s alpha is high for all the 6 components. IAT is a proper tool for evaluating internet addiction in Indian school students. Conclusions: The findings obtained in this study indicate that overall, IAT has adequate psychometric properties for the assessment of internet addiction in Indian school students.

AbstractA vertex coloring of a graph [Formula: see text] is called an exact square coloring of G if any pair of vertices at distance 2 receive distinct colors. The minimum number of colors required by any exact square coloring is called the exact square chromatic number of G and is denoted by [Formula: see text] A set of vertices is called an exact square clique of G if any pair of vertices of the set are at distance 2. The exact square clique number of G, denoted by [Formula: see text] is the maximum cardinality of an exact square clique of G and clearly, [Formula: see text] In this article, we give tight upper bounds of the exact square chromatic number of various standard graph operations, including the Cartesian product, strong product, lexicographic product, corona product, edge corona product, join, subdivision, and Mycielskian of a graph. We also present tight lower bounds of the exact square clique number of these graph operations.

The present research aims to find the groundwater prospective areas by using Geographic Information System and Remote Sensing based frequency ratio technique. The data sets that affect groundwater such as geomorphology, lithology, slope, soil, rainfall, drainage density, lineament density and land use/ land cover were taken under consideration for finding the groundwater prospective areas in the Bundelkhand region, India. Thematic maps of all the above-mentioned factors have been prepared from the remotely sensed data, data taken from the different organizations and departments. The weights of each attribute class of each thematic layer are assigned according to the frequency ratio technique. A total, 799 numbers of spring locations and discharge rate data of 108 numbers of well locations have been taken under consideration for obtaining the frequency ratio of each attribute class of every parameter used and testing the obtained result, respectively. Finally, all layers were combined by raster calculator command in ArcGIS software to develop the map of groundwater prospective zones in the Bundelkhand region. The produced groundwater prospective areas were classified into five different zones such as very high, high, moderate, low and very low prospective zones and verified by actual well yield data.

Abstract Background Newly-qualified doctors in the United Kingdom experience a great deal of stress and have poor wellbeing when compared to more senior counterparts. A number of interventions have been put in place to boost healthcare professionals’ wellbeing, but little is known about interventions aimed to improve the wellbeing of newly-qualified doctors in the United Kingdom. This study aims to systematically review current evidence of interventions which improved the wellbeing of newly-qualified junior doctors in the United Kingdom. Methods Five key electronic databases were searched. Subsequently, reference scanning and citation search was performed. Studies were included if they were conducted from the commencement of the Foundation Programme in 2004, until 2019. In addition, studies had to be performed on junior doctors: working in the United Kingdom and within their first five years post-qualification and have a quantitative outcome. Studies which did not meet these criteria were excluded. Quality was assessed using the modified Newcastle-Ottawa scale. Bias was not formally assessed using a standardised tool. Results Seven papers met the inclusion criteria and identified three main types of interventions: mentorship, mindfulness and clinical preparation interventions. The majority of included studies reported a positive result from the performed intervention, suggesting these to be beneficial in improving junior doctor wellbeing, and thereby reducing anxiety and stress levels. However, most of the studies used small sample sizes. Conclusions This review reveals that there is dearth of evidence on the effectiveness of intervention to improve the wellbeing of newly-qualified doctors in the United Kingdom. Most of the identified interventions focused on relieving stress and anxiety inherent within newly-qualified doctors’ training programmes. However, wellbeing interventions need to take into cognisance all the factors which impact on wellbeing, particularly job-related factors. We recommend that future researchers implement large-scale holistic interventions using appropriate research methods. Systematic review registration: PROSPERO CRD42019127341.

Background. There is limited documentation of hematogenous transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in non–lung transplants from infected donors to uninfected recipients. Methods. We analyzed 16 recipients (7 liver, 9 kidney) transplanted from SARS-CoV-2 nucleic acid test+ deceased donors from December 25, 2021, to February 28, 2022, who were followed-up for at least 90 d. Primary outcomes included coronavirus disease 2019–positivity, allograft loss, and all-cause mortality. Secondary outcomes included biopsy-proven rejection (BPAR), donor-specific antibodies, delayed graft function, and opportunistic infections. Unlike previous studies, we followed the recipients clinically with the intent to treat if they developed SARS-CoV-2 symptoms. Results. All donors were SARS-CoV-2 polymerase chain reaction–positive 72 h before donation. No recipients developed SARS-CoV-2 infection. The nadir serum creatinine and estimated glomerular filtration rate were 1.33 mg/dL and 64 mL/min/1.732 m2 for kidney transplantation (KTx) respectively. The median alanine transaminase was 14.5 IU/L, aspartate aminotransferase 13 IU/L, and alkaline phosphatase 74 IU/L. Two KTx patients lost allograft, and 1 liver transplantation patient died with a failed allograft. However, this was unrelated to their SARS-CoV-2–positive donor status. One BPAR in the liver transplantation was treated with steroids. No donor-specific antibodies or BPAR were reported in the KTx. Six KTx patients experienced delayed graft function, and 4 are off dialysis. Two KTx patients developed cytomegalovirus infection because of an error in reporting the cytomegalovirus serostatus by the donor center. We did not do serial testing for SARS-CoV-2 by polymerase chain reaction, imaging, or cycle threshold score pre- or posttransplant for donor/recipient and had comparable outcomes with previous studies. Conclusions. Because of the low risk of transmission, serial testing might not be necessary and, thus, could be reciprocated at small-volume transplant centers.

Background: Among persons with schizophrenia (PwS), tobacco use is higher in comparison to the general population, contributing to greater morbidity and mortality. Pharmacological interventions combined with psychosocial interventions are effective in tobacco cessation. While the effectiveness of extant psychosocial interventions—when used in isolation—seems limited, developing better combinations of interventions could help treatment providers deliver tobacco cessation services to PwS at different stages of motivation to quit. We aimed to develop a personalized tobacco cessation intervention package (PTCIP) for PwS. Methods: The stage-based intervention package was developed through a systematic review of interventions for tobacco cessation, the authors’ clinical experience, and expert validation. The components of the intervention package, developed for PwS visiting the outpatient psychiatric department, were retained, removed, or added based on the content validity ratio (CVR). Results: The final components included brief advice, principles of motivational interviewing, psychoeducation, decisional balance matrix, positive reinforcement, offering various treatment options, personalized feedback using a smoking-risk calculator, and prediction of cardiovascular risk using the WHO package of essential noncommunicable disease (PEN). The delivery of the intervention package was refined based on pilot testing in eight participants. Conclusion: The tailored package was designed to be delivered by a mental health professional as a single comprehensive 40 min to 45 min face-to-face session, integrated with routine follow-up visits, followed by two telephonic conversations in the second and third week of the initial session. The package needs to be tested in a randomized controlled trial for its effectiveness.

Background: Anxiety disorders have high prevalence in diabetes patients and low-middle income countries like India. Research has provided evidence about biofeedback effectiveness on stress-related psychophysiological parameters. This study aimed to verify the impact of GSR biofeedback relaxation on stress-related psychophysiological parameters (galvanic skin resistance, stress, and anxiety) among type II diabetes patients with high levels of anxiety. Methods: The present study was a single-blinded randomized controlled trial. Initially, 228 type II diabetes patients were assessed with the state trait anxiety inventory (STAI). Seventy participants identified as having high anxiety with STAI scores above the 75th percentile were invited to participate. Patients were randomly divided into a biofeedback relaxation and a sham-control group. Participants of the biofeedback group received training on how to use the GSR biofeedback device for management of stress parameters for twenty 30-minute sessions. The sham-control group received no intervention. Both groups were assessed before and after the biofeedback relaxation training program. The results of the STAI, GSR, and the inventory of stress for type II diabetes patients were compared. SPSS 16 version was used for analysis. Results: The biofeedback group reported a significant change in the state of anxiety (t=5.089; p

Summary: Despite prolific efforts to characterize the antibody response to human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) mono-infections, the response to chronic co-infection with these two ever-evolving viruses is poorly understood. Here, we investigate the antibody repertoire of a chronically HIV-1/HCV co-infected individual using linking B cell receptor to antigen specificity through sequencing (LIBRA-seq). We identify five HIV-1/HCV cross-reactive antibodies demonstrating binding and functional cross-reactivity between HIV-1 and HCV envelope glycoproteins. All five antibodies show exceptional HCV neutralization breadth and effector functions against both HIV-1 and HCV. One antibody, mAb688, also cross-reacts with influenza and coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We examine the development of these antibodies using next-generation sequencing analysis and lineage tracing and find that somatic hypermutation established and enhanced this reactivity. These antibodies provide a potential future direction for therapeutic and vaccine development against current and emerging infectious diseases. More broadly, chronic co-infection represents a complex immunological challenge that can provide insights into the fundamental rules that underly antibody-antigen specificity.

The recent Chandra-JWST discovery of a quasar in the z ≈ 10.1 galaxy UHZ1 reveals that accreting supermassive black holes were already in place 470 million years after the Big Bang. The Chandra X-ray source detected in UHZ1 is a Compton-thick quasar with a bolometric luminosity of L _bol ∼ 5 × 10 ^45 erg s ^−1 , which corresponds to an estimated black hole (BH) mass of ∼4 × 10 ^7 M _⊙ , assuming accretion at the Eddington rate. JWST NIRCAM and NIRSpec data yield a stellar mass estimate for UHZ1 comparable to its BH mass. These characteristics are in excellent agreement with prior theoretical predictions for a unique class of transient, high-redshift objects, overmassive black hole galaxies (OBGs) by Natarajan et al., that harbor a heavy initial black hole seed that likely formed from the direct collapse of the gas. Given the excellent agreement between the observed multiwavelength properties of UHZ1 and theoretical model template predictions, we suggest that UHZ1 is the first detected OBG candidate. Our assertion rests on multiple lines of concordant evidence between model predictions and the following observed properties of UHZ1: its X-ray detection and the estimated ratio of the X-ray flux to the IR flux, which is consistent with theoretical expectations for a heavy initial BH seed; its high measured redshift of z ≈ 10.1, as predicted for the transient OBG stage (9 < z < 12); the amplitude and shape of the detected JWST spectral energy distribution (SED) between 1 and 5 μ m, which is in very good agreement with simulated template SEDs for OBGs; and the extended JWST morphology of UHZ1, which is suggestive of a recent merge and is also expected for the formation of transient OBGs. As the first OBG candidate, UHZ1 provides compelling evidence for the formation of heavy initial seeds from direct collapse in the early Universe.

Fueling and feedback couple supermassive black holes (SMBHs) to their host galaxies across many orders of magnitude in spatial and temporal scales, making this problem notoriously challenging to simulate. We use a multi-zone computational method based on the general relativistic magnetohydrodynamic (GRMHD) code KHARMA that allows us to span 7 orders of magnitude in spatial scale, to simulate accretion onto a non-spinning SMBH from an external medium with a Bondi radius of R _B ≈ 2 × 10 ^5 GM _• / c ^2 , where M _• is the SMBH mass. For the classic idealized Bondi problem, spherical gas accretion without magnetic fields, our simulation results agree very well with the general relativistic analytic solution. Meanwhile, when the accreting gas is magnetized, the SMBH magnetosphere becomes saturated with a strong magnetic field. The density profile varies as ∼ r ^−1 rather than r ^−3/2 and the accretion rate $\dot{M}$ is consequently suppressed by over 2 orders of magnitude below the Bondi rate ${\dot{M}}_{{\rm{B}}}$ . We find continuous energy feedback from the accretion flow to the external medium at a level of $\sim {10}^{-2}\dot{M}{c}^{2}\sim 5\,\times \,{10}^{-5}{\dot{M}}_{{\rm{B}}}{c}^{2}$ . Energy transport across these widely disparate scales occurs via turbulent convection triggered by magnetic field reconnection near the SMBH. Thus, strong magnetic fields that accumulate on horizon scales transform the flow dynamics far from the SMBH and naturally explain observed extremely low accretion rates compared to the Bondi rate, as well as at least part of the energy feedback.

The James Webb Space Telescope is now detecting early black holes (BHs) as they transition from “seeds” to supermassive BHs. Recently, Bogdan et al. reported the detection of an X-ray luminous supermassive BH, UHZ-1, with a photometric redshift at z > 10. Such an extreme source at this very high redshift provides new insights on seeding and growth models for BHs given the short time available for formation and growth. Harnessing the exquisite sensitivity of JWST/NIRSpec, here we report the spectroscopic confirmation of UHZ-1 at z = 10.073 ± 0.002. We find that the NIRSpec/Prism spectrum is typical of recently discovered z ≈ 10 galaxies, characterized primarily by star formation features. We see no clear evidence of the powerful X-ray source in the rest-frame UV/optical spectrum, which may suggest heavy obscuration of the central BH, in line with the Compton-thick column density measured in the X-rays. We perform a stellar population fit simultaneously to the new NIRSpec spectroscopy and previously available photometry. The fit yields a stellar-mass estimate for the host galaxy that is significantly better constrained than prior photometric estimates ( ${M}_{\star }\sim {1.4}_{-0.4}^{+0.3}\times {10}^{8}$ M _⊙ ). Given the predicted BH mass ( M _BH ∼ 10 ^7 –10 ^8 M _⊙ ), the resulting ratio of M _BH / M _⋆ remains 2 to 3 orders of magnitude higher than local values, thus lending support to the heavy seeding channel for the formation of supermassive BHs within the first billion years of cosmic evolution.

We present a robust sample of very high redshift galaxy candidates from the first epoch of JWST/NIRCam imaging from the Next Generation Deep Extragalactic Exploratory Public (NGDEEP) survey. The NGDEEP NIRCam imaging, spanning 9.7 arcmin ^2 in the Hubble Ultra Deep Field Parallel Field 2, reaches m = 30.4 (5 σ , point-source, 2″ diameter apertures corrected to total) in F277W, making it the deepest public JWST GO imaging data set to date. We describe our detailed data reduction process of the six-filter broadband JWST/NIRCam imaging, incorporating custom corrections for systematic effects to produce high-quality calibrated images. Using robust photometric redshift selection criteria, we identify a sample of 38 z ≳ 9 galaxy candidates. These objects span a redshift range of z = 8.5–15.8 and apparent magnitudes of m _F277W = 27–30.5 AB mag, reaching ∼1.5 mag deeper than previous public JWST imaging surveys. We calculate the rest-frame ultraviolet luminosity function at z ∼ 9 and 11 and present a new measurement of the luminosity function faint-end slope at z ∼ 11. We find a faint-end slope of α = −2.5 ± 0.4 and −2.2 ± 0.2 at z ∼ 9 and 11, respectively. This is consistent with no significant evolution in the faint-end slope and number density from z = 9 to 11. Comparing our results with theoretical predictions, we find that some models produce better agreement at the faint end than the bright end. These results will help to constrain how stellar feedback impacts star formation at these early epochs.

We look for simulated star-forming linear features such as the one recently discovered by van Dokkum et al. in the cosmological hydrodynamical simulation ASTRID . Among the runaway black holes in ASTRID , none are able to produce clear star-forming wakes. Meanwhile, flyby encounters, typically involving a compact galaxy (with a central black hole) and a star-forming galaxy (with a duo of black holes), reproduce remarkably well many of the key properties (length and linearity, recent star formation, etc.) of the observed star-forming linear feature. We predict that the feature will persist for approximately 100 Myr in such a system and hence constitute a rare event. The feature contains a partly stripped galaxy (with M _gal = 10 ^9 –10 ^10 M _⊙ ) and a dual black hole system ( M _BH = 10 ^5 –10 ^7 M _⊙ ) in its brightest knot. The X-ray emission from AGN in the knot should be detectable in such systems. After 100–200 Myr from the first flyby, the galaxies merge, leaving behind a triple black hole system in a (still) actively star-forming early-type remnant of mass ∼5 × 10 ^10 M _⊙ . Follow-up JWST observations may be key for revealing the nature of these linear features by potentially detecting the older stellar populations constituting the bright knot. Confirmation of such detections may therefore help discriminate a flyby encounter from a massive black hole wake to reveal the origin of such features.

The NANOGrav 15 yr data set shows evidence for the presence of a low-frequency gravitational-wave background (GWB). While many physical processes can source such low-frequency gravitational waves, here we analyze the signal as coming from a population of supermassive black hole (SMBH) binaries distributed throughout the Universe. We show that astrophysically motivated models of SMBH binary populations are able to reproduce both the amplitude and shape of the observed low-frequency gravitational-wave spectrum. While multiple model variations are able to reproduce the GWB spectrum at our current measurement precision, our results highlight the importance of accurately modeling binary evolution for producing realistic GWB spectra. Additionally, while reasonable parameters are able to reproduce the 15 yr observations, the implied GWB amplitude necessitates either a large number of parameters to be at the edges of expected values or a small number of parameters to be notably different from standard expectations. While we are not yet able to definitively establish the origin of the inferred GWB signal, the consistency of the signal with astrophysical expectations offers a tantalizing prospect for confirming that SMBH binaries are able to form, reach subparsec separations, and eventually coalesce. As the significance grows over time, higher-order features of the GWB spectrum will definitively determine the nature of the GWB and allow for novel constraints on SMBH populations.