bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-world effects of antidepressants for depressive disorder in primary care: population-based cohort study
Authors: De Crescenzo Franco , De Giorgi Riccardo , Garriga Cesar , Liu Qiang , Fazel Seena , Efthimiou Orestis , Hippisley-Cox Julia , Cipriani Andrea
Published: December 2024

Background

Antidepressants’ effects are established in randomised controlled trials (RCTs), but not in the real world.

Aims

To investigate real-world comparative effects of antidepressants for depression and compare them with RCTs.

Method

We performed a cohort study based on the QResearch database. We included people with a newly recorded diagnosis of depression, exposed to licensed antidepressants in the UK. We assessed all-cause dropouts (acceptability), dropouts for adverse events (tolerability), occurrence of at least one adverse event (safety), and response and remission on the Patient Health Questionnaire (PHQ)-9 (effectiveness) at 2 and 12 months. Logistic regressions were used to compute adjusted-odds ratio (aOR) with 99% CIs, assessing the associations between exposure to each antidepressant against fluoxetine (comparator) and outcomes of interest. We compared estimates from the real world with RCTs using ratio-of-odds ratio (ROR) with 95% CI.

Results

A total of 673 177 depressed people were studied: females 57.1%, mean age 42.8 (s.d. 17.7) years, mean baseline PHQ-9 17.1 (s.d. 5.0) (moderately severe depression). At 2 months, antidepressant acceptability was 61.4%, tolerability 94.4%, safety 54.5%, PHQ-9 decreased to 12.3 (s.d. 6.5). At 12 months, acceptability was 12.3%, tolerability 87.5%, safety 28.8%, PHQ-9 12.9 (s.d. 6.8). In the short and long term, tricyclics, mirtazapine and trazodone were worse than fluoxetine for most outcomes; citalopram had better acceptability than fluoxetine (aOR 0.95; 99% CI 0.92, 0.97), sertraline had lower tolerability (aOR 1.12; 99% CI 1.06, 1.18), and both citalopram and sertraline had lower safety (aOR 1.17 and 1.25, respectively). In the long term, citalopram had better acceptability (aOR 0.78; 99% CI 0.76, 0.81) and effectiveness (aOR 1.12 for both response and remission), but worse tolerability (aOR 1.09; 99% CI 1.06, 1.13) and safety (aOR 1.12; 99% CI 1.08, 1.16). Observational and randomised data were similar for citalopram and sertraline, while there was some difference for drugs less prescribed in the real world.

Conclusions

Antidepressants showed low acceptability, moderate-to-high tolerability and safety, and small-to-moderate effectiveness in the real world. Real-world and RCT estimates showed similar findings only when the analyses were carried out using large datasets; otherwise, the results diverged.
Mesogenic Architectures for Advanced Drug Delivery: Interrogating Lyotropic and Thermotropic Liquid Crystals
Authors: Govindan Induja , Paul Angeeta , Rama Annamalai , Kailas Anjana A. , Abutwaibe K. A. , Annadurai Thamizharasan , Naha Anup
Published: December 2024

The possibility of precisely regulating and targeting drug release with mesophase or Liquid crystal drug delivery systems has drawn much attention recently. This review offers a thorough investigation of liquid crystal drug delivery systems with an emphasis on their mesogenic architecture. It describes the various liquid crystal forms such as thermotropic and lyotropic liquid crystals and their applicability in advanced drug delivery. Liquid crystals are used as excellent carriers due to their distinctive characteristics, such as stimuli-responsive drug delivery and sustained release patterns. Comprehending the materials that form mesophase provides insight into their distinct physiochemical characteristics and their use in drug delivery. This review highlights the important role lyotropic and thermotropic liquid crystals play in drug delivery, underscoring their considerable potential. The transition of thermotropic liquid crystals from their conventional technological applications to drug delivery has been studied. Nonetheless, a few challenges still need to be addressed, including formulation strategy refinement, regulating release rates, maximising the loading of hydrophilic drugs, and storage stability. In the pharmaceutical field, addressing these issues will open the door to a revolutionary paradigm that will revolutionise therapeutic outcomes and improve patient care.

Graphical Abstract
Insights into coherently controlled Fizeau light dragging in five-level atomic medium
Authors: Khan Ubaidullah , Khesro Amir , Ali Riaz , Ali Wahid , Amina  , Akbar Jehan , Usman Muhammad , EL-Gawaad N. S. Abd
Published: December 2024

We address the coherent regulation of Fizeau's light dragging effect in a five-level atomic medium using the exploitation of joint strong control and weak probing fields. The strength of Fizeau's light dragging, as well as the phase velocity and group index, exhibit a strong reliance upon the detuning of the probing type field and the associated Rabi type frequencies of the control fields. The maximum coefficient for Fizeau's light dragging is determined to be ±500. This phenomenon significantly affects the phase along with the group velocities and induces a phase shift in light pulses propagating through the medium. Besides, the phase shift with maximum strength of light pulse in the medium is found to be ±0.08 radians. Finally, it is important to note that our findings hold practical implications for applications such as interferometry, imaging coding, and the development of cloaking devices.
Challenges of Motherhood for Anesthesiologists: A Scoping Review
Authors: Mergler Blake D. , Patel Riya U. , Iyer Shivani , Chae Rebecca S. , Gluch Joan I. , Mergler Reid J. , Vail Emily A. , Duffy Caoimhe C.
Published: December 2024

Despite advancements in gender representation, female anesthesiologists continue to encounter challenges in career advancement that may be further impacted by motherhood. This scoping review examines personal and systemic barriers and facilitators to career advancement for anesthesiologists facing infertility, pregnancy, and childcare. The review identified 22 relevant studies across five themes: the timing of pregnancy and parental leave, breastfeeding and lactation needs, childcare and gender norms, job reentry and career advancement opportunities, and work-life balance and physician well-being. Recommendations from these studies include establishing clear parental leave policies, providing adequate lactation spaces and protected break times, addressing gender disparities in leadership roles, and prioritizing physician well-being. To implement these recommendations effectively, institutions and departments should develop and disseminate role-specific policies that promote career advancement and satisfaction through equitable support of pregnant and parent anesthesiologists.
Molecular characterization and sub-retinal transplantation of hypoimmunogenic human retinal sheets in a minipig model of severe photoreceptor degeneration
Authors: Barabino Andrea , Mellal Katia , Hamam Rimi , Polosa Anna , Griffith May , Bouchard Jean-François , Kalevar Ananda , Hanna Roy , Bernier Gilbert
Published: December 2024

Retinal degenerative diseases affect millions of people worldwide, and legal blindness is generally associated with the loss of cone photoreceptors located in the central region of the retina called the macula. Currently, there is no treatment to replace the macula. Addressing this unmet need, we employed control isogenic and hypoimmunogenic induced pluripotent stem cell lines to generate spontaneously polarized retinal sheets (RSs). RSs were enriched in retinal progenitor and cone precursor cells, which could differentiate into mature S- and M/L-cones in long-term cultures. Single-cell RNA-seq analysis showed that RSs recapitulate the ontogeny of the developing human retina. Isolation of neural rosettes for sub-retinal transplantation effectively eliminated unwanted cells such as RPE cells. In a porcine model of chemically induced retinal degeneration, grafts integrated the host retina and formed a new, yet immature, photoreceptor layer. In one transplanted animal, functional and immunohistochemical assays suggest that grafts exhibited responsiveness to light stimuli and established putative synaptic connections with host bipolar neurons. This study underscores the potential and challenges of RSs for clinical applications.
Public views of coronavirus science and scientists: findings from a cross-sectional survey
Authors: Gooberman-Hill Rachael , Taylor Michelle L. , Maude Ulrika , Yardley Lucy , Huxtable Richard , Stubbs Jo , Peters Tim J.
Published: December 2024

Background Throughout the coronavirus pandemic, references to scientific findings have permeated public-facing communications. Understanding how members of the public view science, scientists and scientific uncertainty should enhance approaches to communication and individuals’ decisions to engage with public health measures, including restrictions and vaccination programmes. This article provides descriptive statistics regarding public views and their univariable associations with key variables: age, gender, ethnicity, keyworker status, shielding status, caring responsibilities, and coronavirus exposure. Methods A survey was conducted on our behalf by YouGov in November 2020. The survey asked about: level of public trust in scientists and scientific information; changes in trust between March and November 2020; views about communication of scientific uncertainty; confidence in the accuracy of scientific findings; and views about whether public information accurately represents coronavirus science. Results The sample comprised 2,025 individuals in England; 40.5% were ≥55 years old, 51.1% were female; 12.3% identified as members of an ethnic minority/mixed ethnicity. Trust was highest among older respondents and those who identified as of white ethnicity. The concurrent (November 2020) levels of reported trust in scientific information about coronavirus were generally lower than those reported retrospectively for the pandemic’s start (March 2020). There was higher trust and positivity about science among people who had been shielding and among those who had not contracted coronavirus. Around half of respondents did not think that the uncertainty in science was conveyed much or at all, most were confident in the accuracy of coronavirus science, and around half thought that public information was a true representation of the science. Conclusions Our study indicates that there is room to improve trust and communication in science. As well as multivariable analyses to explore interrelationships, further research could examine reasons behind change in trust over time and any patterns due to age, ethnicity, and shielding status.
Ultrasonography in the Diagnosis of Bronchiolitis: Evaluation of Effectiveness and Application in Clinical Practice
Authors: Zalewa Karolina , Olszak Joanna , Kapłan Wojciech , Orłowska Dominika , Bartoszek Lidia , Poleszczuk Mikołaj , Poleszczuk Karol , Czuba Anna , Milewska Alicja
Published: December 2024

Introduction and Purpose
This study investigates the effectiveness and clinical applicability of lung ultrasound (LUS) in diagnosing acute bronchiolitis. Bronchiolitis is challenging to diagnose due to symptom overlap with other respiratory infections and varying clinical presentations. While conventional diagnosis relies on patient history and physical examination, LUS has emerged as a promising, non-invasive tool that may improve diagnostic accuracy and provide valuable insights into disease severity without the radiation risks associated with X-rays.
Material and MethodsThis review is based on articles from the PubMed database, covering the years 2012-2024, using keywords: bronchiolitis, LUS, lung ultrasound.
ResultsThe study found that LUS demonstrated high sensitivity and specificity for identifying bronchiolitis-related lung abnormalities, including areas of consolidation and interstitial involvement. A strong association was observed between ultrasound scores and clinical severity, with elevated scores correlating with increased need for respiratory support. LUS was more effective than conventional chest X-rays for detecting consolidations over 1 cm and predicting oxygenation issues in critically ill patients.
ConclusionsLUS proves to be a valuable diagnostic tool for bronchiolitis, providing a safe, radiation-free alternative to traditional imaging and yielding reliable information on disease severity. Its ease of use, combined with its predictive value in identifying children at risk for respiratory complications, highlights LUS as a practical method for bedside assessment. Moreover, advancements in AI-supported LUS analysis hold potential for reducing operator dependency, enhancing diagnostic consistency, and improving workflow efficiency in emergency settings. Integrating LUS into routine practice could thus enhance care for pediatric bronchiolitis patients, supporting more accurate, timely diagnoses and targeted treatment interventions.
Delegation with Technology Migration: An Empirical Analysis of Mobile Virtual Network Operators
Authors: Zou Fan , Dong Yan , Hu Kejia , Venkataraman Sriram
Published: December 2024

This study examines the impact of mobile virtual network operators (MVNOs) on the performance of mobile network operators (MNOs) in the presence of overlapping generations of wireless mobile network technologies (2G and 3 G). MVNOs distribute MNOs’ mobile services to customers without owning any spectrum or network infrastructures, either as a subsidiary (branded MVNOs) or delegated under wholesale agreements with MNOs (third-party MVNOs). We investigate MVNO value chain governance, that is, delegation, in the context of overlapping generations of technologies. Leveraging a proprietary data set, we design a quasi-experiment to analyze the impact of branded and third-party MVNOs in 2G and 3 G market expansion. Using first a difference-in-differences analysis and then dynamic propensity score matching, we find that an MNO’s 2G market share increases if the MNO launches a third-party MVNO, whereas its 3 G market share increases if it launches a branded MVNO. More importantly, the positive effects of branded MVNOs diminish over time, but those of third-party MVNOs become stronger over time. For managers challenged by managing overlapping generations of technologies, it is important to customize value chain governance for market expansion: to create branded MVNOs to explore new mobile technologies, and to delegate to third-party MVNOs to exploit existing technology markets when the technology market is mature.

This paper was accepted by Jayashankar Swaminathan, operations management.

Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2021.01832 .
Don’t throw the colonial text out with its ideology!: Recruiting a colonial text to do decolonial work on a university academic literacy course
Authors: Torquato Cloris , Arend Moeain , Hunma Aditi
Published: December 2024

Since 2015, South African universities have undergone a major overhaul, with students nationwide calling for curriculum reform to introduce texts and approaches that do not perpetuate colonial ideologies. This presented an opportunity to shed untransformed ways of knowing, and recent publications in the region reflect this impetus. It is in this climate, in 2019, that our course, Writing Across Borders, was launched to foster critical literacy practices, exposing students to diverse texts, including a history textbook published in 1909. Our use of this textbook presently could be questioned. We argue, however, that instead of throwing the colonial text out with its ideology, it can be recruited differently to reveal its problematic constructions of race and contradictions. This article models the class discussions around the history textbook, applying a critical discourse analysis lens, which allows for multi-layered analysis, and surfaces asymmetries of power that created the conditions for social injustices in colonial and postcolonial contexts. The analysis demonstrates that meaning does not reside in the text alone, but in how it is used to achieve its decolonial meaning potential, and to invite us all to unlearn our enduring racial biases. It thus offers us pedagogical possibilities by harnessing colonial texts differently.
Introduction: Jim Siegel Reappears
Authors: Barker Joshua , Rafael Vicente , Rutherford Danilyn
Published: December 2024

Abstract: This article introduces a special issue of the journal INDONESIA that both honors and reckons with the work of Jim Siegel, an anthropologist and Indonesianist whose highly original scholarship and unique style of mentorship have left a lasting impact on so many of his students, colleagues, and others. The article provides a brief biographical sketch of Siegel and identifies some of the key themes that emerge from the articles, interviews, and personal reflections that make up the issue: the approach to teaching and mentorship that continually pushes at the limits of understanding; the interweaving of philosophy and anthropology; the ethic of openness to otherness; and more.
The Jokes of Jim Siegel
Authors: Rafael Vicente L.
Published: December 2024

Abstract: Jim Siegel has a certain fondness for jokes. In this essay, I look at distinct moments when his interest in humor becomes apparent: in his often-vexed relationship with the Anthropology Department at Cornell; his ethnographic work in Indonesia; and his obsession with the price of goods in Paris.
Scheduled lightpath demand provisioning in fiber space division multiplexing optical networks
Authors: Han Shudan , Li Yongcheng , Shen Gangxiang , Mukherjee Biswanath
Published: December 2024

Space division multiplexing (SDM) and spatial super-channel (Spa SCh) technology offer scalable solutions to meet the increasing capacity demands in optical networks. This study focuses on multi-fiber optical networks integrated with the innovative Spa SCh technology, which creates different granularities of Spa SChs by spatially combining the same spectrum across multiple fibers, known as fiber-SDM (FSDM). Most existing studies have concentrated on provisioning dynamic or static lightpath demands in FSDM networks. However, for several applications in real-world networks, scheduled lightpath demands—where setup and teardown times are pre-determined—are more common. To address this, we consider the provisioning of scheduled lightpath demands in FSDM networks and aim to solve the routing, fiber, spectrum, and time-slot assignment (RFSTA) problem for these demands. We propose two integer linear programming (ILP) models: one optimizing only the spectrum resource utilization (SRU) and the other jointly optimizing both SRU and capital expenditure (CAPEX). In addition, we develop several efficient heuristic algorithms for large-scale optical networks, based on the concepts of the spatial spectrum window (SSW), SSW plane, and time-slot window (TW). Furthermore, an evolutionary joint optimization strategy is introduced to explore optimal Spa SCh configurations, aiming to jointly optimize network SRU and CAPEX. Simulation results demonstrate that the proposed algorithms closely match the performance of ILP models in small networks. Among the heuristic approaches, the adaptive least-load algorithm performs best under an optimal Spa SCh configuration, which bundles half of the fibers to form link fiber bundles.
Pre-calculated space-ground integrated structure (P-SGIS) against link cut set (LCS) failures in space-ground integrated optical networks
Authors: Li Xin , Liu Yu , Liu Tianhao , Li Daixuan , Yan Xuhao , Zhao Chenyu , Ruan Feiyang , Huang Shanguo
Published: December 2024

Fiber link failure is a common and frequent failure type in terrestrial optical networks (TONs). To guarantee the stable operation of the TON against single or multi-link failures, various kinds of survivability technologies have been proposed. Although these survivability technologies are effective in many cases, a link cut set (LCS), which is a set of fiber links whose simultaneous failures can disconnect the TON, presents an extreme situation of network partitioning that these technologies cannot address. Recently, the satellite network has obtained rapid development and various types of satellite constellations are being constructed. Moreover, the laser inter-satellite link (LISL) is studied deeply and verified widely. The satellite optical network (SON) is gradually formed and can be integrated with the TON together into the space-ground integrated optical network (SGION). In the SGION, the LCS failure in the TON can be addressed by the SON. This paper focuses on space-ground integrated protection. A pre-calculated space-ground integrated structure (P-SGIS) is designed. “Pre-calculated” refers to extracting reliable, low-redundant backup protection structures in advance from the physical topology of the SGION, based on prior knowledge, such as satellite movement regularity, failure distribution, and so on. Heuristic algorithms are developed for P-SGIS construction and backup resource reservation. Numerical results show that the P-SGIS-based protection scheme has high resource efficiency and protection success rate.
Mechanically reconfigurable cavity filters using liquid metals in the W-band
Authors: Gao Qihan , Niu Qiang , Li Yangyang , Hu Jiarui , Peng Yizhao , Zou Bin , Yang Yuping
Published: December 2024

The high adaptability and flexibility of reconfigurable cavity filters (RCFs) provide a compelling solution for signal modulation in communication systems. However, current reports on these filters are predominantly concentrated within the frequency range of a few GHz. As communication frequencies continue to escalate, there is a pressing need for filters that can operate at higher frequencies. This study presents a mechanical RCF operating in the W-band (75-110 GHz) that address the need for high-frequency cavity filters. The reconfigurability of the filter is enhanced by adjusting the height of the liquid metal posts and interchanging different liquid metal (LM) media, thereby augmenting its tuning flexibility. During the experiment, we observed the potential dispersion effects of the LMs near 100 GHz, which were hypothetically validated. Finally, we tested the performance of the RCF with single or double LM tubes using a vector network analyzer to achieve consistency between the experimental and simulated results. This study offers a unique solution for sub-terahertz communication systems with critical requirements for dynamic filtering capabilities.
Research on the DF-TSOM method for detecting subsurface defects of optical components
Authors: Wang Na , Zhou Weihu , Song Xiaojiao , Wang Dezhao , Liu Lituo
Published: December 2024

In response to the growing need for detecting subsurface defects at the hundred-nanometer scale, this study introduces what we believe to be a novel dark field through-focus scanning optical microscopy (DF-TSOM) technique. Subsurface defect samples were prepared with a depth of 100 µm and diameters of 1 µm, 0.4 µm, 0.2 µm, and 0.1 µm for experiments. Results demonstrate that DF-TSOM successfully detects subsurface defects with diameters 0.1 µm, a feat unattainable with traditional TSOM, which failed to accurately detect subsurface defects with diameters 0.4 µm. DF-TSOM improves the contrast by approximately 10 times compared to traditional TSOM when the subsurface defect diameter is 1 µm. This study presents a promising new approach for the detection of subsurface defects in transparent materials, offering advantages such as high sensitivity, enhanced contrast, a simplified hardware setup, and the potential for online detection.
All-reflective freeform microscope objective for ultra-broadband microscopy
Authors: Bauer Aaron , Rolland Jannick P. , Clark Stephan , Potma Eric , Hanninen Adam
Published: December 2024

Conventional refractive microscope objective lenses have limited applicability to a range of imaging modalities due to the dispersive nature of their optical elements. Designing a conventional refractive microscope objective that provides well-corrected imaging over a broad spectral range can be challenging, if not impossible. In contrast, reflective optics are inherently achromatic, so a system composed entirely of reflective elements is free from chromatic aberrations and, as a result, can image over an ultra-wide spectral range with perfect color correction. This study explores the design space of unobscured high numerical aperture, all-reflective microscope objectives. In particular, using freeform optical elements we obviate the need for a center obscuration, rendering the objective’s modulation transfer function comparable to that of refractive lens systems of similar numerical aperture. We detail the design process of the reflective objective, from determining the design specifications to the system optimization and sensitivity analysis. The outcome is an all-reflective freeform microscope objective lens with a 0.65 numerical aperture that provides diffraction-limited imaging and is compatible with the geometric constraints of commercial microscope systems.
Public surface disinfection every 2 hours can reduce the infection risk of norovirus in airports up to 83%
Authors: Zhang Nan , Zhuang Linan , King Marco-Felipe , Qian Hua , Zhu Min
Published: December 2024

Norovirus, primarily transmitted via fomite route, poses a significant threat to global public health and the economy. Airports, as critical transportation hubs connecting people from around the world, has high potential risk of norovirus transmission due to large number of public surfaces. A total of 21.3 hours of video episodes were recorded across nine functional areas at the airport, capturing 25,925 touches. A surface transmission model based on a Markov chain was developed. Using the beta-Poisson dose-response model, the infection risk of norovirus and the effectiveness of various interventions in different airports’ areas were quantified. Without any preventive measures, restaurants at airports exhibited the highest risk of norovirus transmission, with an infection probability of 8.8×10−3% (95% CI, 1.5×10−3% -2.1×10−2%). This means approximately 4.6 (95% CI, 0.8–10.9) out of 51,494 passengers who entered the restaurants would be infected by an infected passenger. Comparing with no surface disinfection, disinfecting public surfaces every 2 hours can reduce the risk of norovirus infection per visit to the airport by 83.2%. In contrast, comparing with no hand washing, handwashing every 2 hours can reduce the infection risk per visit to the airport by only 2.0%, making public surface disinfection significantly more effective than handwashing. If the mask-wearing rate increases from 0% to 50%, the infection risk of norovirus would be decreased by 48.0% (95% CI, 43.5–52.3%). Furthermore, using antimicrobial copper/copper-nickel alloy coatings for most public surfaces could reduce the infection risk by 15.9%-99.2%.
Modelling the effectiveness of antiviral treatment strategies to prevent household transmission of acute respiratory viruses
Authors: Zaaraoui Hind , Schumer Clarisse , Duval Xavier , Hoen Bruno , Opatowski Lulla , Guedj Jérémie
Published: December 2024

Households are a major driver of transmission of acute respiratory viruses, such as SARS-CoV-2 or Influenza. Until now antiviral treatments have mostly been used as a curative treatment in symptomatic individuals. During an outbreak, more aggressive strategies involving pre- or post-exposure prophylaxis (PrEP or PEP) could be employed to further reduce the risk of severe disease but also prevent transmission to household contacts. In order to understand the effectiveness of such strategies and the factors that may modulate them, we developed a multi-scale model that follows the infection at both the individual-level (viral dynamics) and the population-level (transmission dynamics) in households. Using a simulation study we explored different antiviral treatment strategies, evaluating their effectiveness on reducing the transmission risk and the virological burden in households for a range of virus characteristics (e.g., secondary attack rate—SAR, or time to peak viral load). We found that when the index case can be identified and treated before symptom onset, both transmission and virological burden are reduced by > 75% for most SAR values and time to peak viral load, with minimal benefit to treat additionally household contacts. While treatment initiated after index symptom onset does not reduce the risk of transmission, it can still reduce the virological burden in the household, a proxy for severe disease and subsequent transmission risk outside the household. In that case optimal strategies involve treatment of both index case and household contacts as PEP, with efficacy > 50% when peak viral load occurs after symptom onset, and 30-50% otherwise. In all the considered cases, antiviral treatment strategies were optimal for SAR ranging 20-60%, and for larger household sizes. This study highlights the opportunity of antiviral drug-based interventions in households during an outbreak to minimize viral transmission and disease burden.
Functional investigation suggests CNTNAP5 involvement in glaucomatous neurodegeneration obtained from a GWAS in primary angle closure glaucoma
Authors: Chakraborty Sudipta , Sarma Jyotishman , Roy Shantanu Saha , Mitra Sukanya , Bagchi Sayani , Das Sankhadip , Saha Sreemoyee , Mahapatra Surajit , Bhattacharjee Samsiddhi , Maulik Mahua , Acharya Moulinath
Published: December 2024

Primary angle closure glaucoma (PACG) affects more than 20 million people worldwide, with an increased prevalence in south-east Asia. In a prior haplotype-based Genome Wide Association Study (GWAS), we identified a novel CNTNAP5 genic region, significantly associated with PACG. In the current study, we have extended our perception of CNTNAP5 involvement in glaucomatous neurodegeneration in a zebrafish model, through investigating phenotypic consequences pertinent to retinal degeneration upon knockdown of cntnap5 by translation-blocking morpholinos. While cntnap5 knockdown was successfully validated using an antibody, immunofluorescence followed by western blot analyses in cntnap5-morphant (MO) zebrafish revealed increased expression of acetylated tubulin indicative of perturbed cytoarchitecture of retinal layers. Moreover, significant loss of Nissl substance is observed in the neuro-retinal layers of cntnap5-MO zebrafish eye, indicating neurodegeneration. Additionally, in spontaneous movement behavioural analysis, cntnap5-MO zebrafish have a significantly lower average distance traversed in light phase compared to mismatch-controls, whereas no significant difference was observed in the dark phase, corroborating with vision loss in the cntnap5-MO zebrafish. This study provides the first direct functional evidence of a putative role of CNTNAP5 in visual neurodegeneration.
Rare but elevated incidence of hematological malignancy after clozapine use in schizophrenia: A population cohort study
Authors: Hu Yuqi , Gao Le , Zhou Lingyue , Liu Wenlong , Wei Cuiling , Liu Boyan , Sun Qi , Tian Wenxin , Chu Rachel Yui Ki , Song Song , Cheng Franco Wing Tak , Chan Joe Kwun Nam , Ng Amy Pui Pui , Lo Heidi Ka Ying , Lee Krystal Chi Kei , Chang Wing Chung , Wong William Chi Wai , Chan Esther Wai Yin , Wong Ian Chi Kei , Chai Yi , Lai Francisco Tsz Tsun
Published: December 2024

Background

Clozapine is widely regarded as a highly efficacious psychotropic drug that is largely underused worldwide. Recent disproportionality analyses and nationwide case-control studies suggested a potential association between clozapine use and hematological malignancy (HM). Nevertheless, the absolute rate difference is not well-established due to the absence of analytic cohort studies. The clinical significance of such a potential risk remains unclear.

Methods and findings

We extracted data from a territory-wide public healthcare database from January 2001 to August 2022 in Hong Kong to conduct a retrospective cohort study of anonymized patients aged 18+ years with a diagnosis of schizophrenia who used clozapine or olanzapine (drug comparator with highly similar chemical structure and pharmacological mechanisms) for 90+ days, with at least 2 prior other antipsychotic use records within both groups. Weighted by inverse probability of treatment (IPTW) based on propensity scores, Poisson regression was used to estimate the incidence rate ratio (IRR) of HM between clozapine and olanzapine users. The absolute rate difference was also estimated. In total, 9,965 patients with a median follow-up period of 6.99 years (25th to 75th percentile: 4.45 to 10.32 years) were included, among which 834 were clozapine users. After IPTW, the demographic and clinical characteristics of clozapine users were comparable to those of olanzapine users. Clozapine users had a significant weighted IRR of 2.22 (95% confidence interval (CI) [1.52, 3.34]; p < 0.001) for HM compared to olanzapine users. The absolute rate difference was estimated at 57.40 (95% CI [33.24, 81.55]) per 100,000 person-years. Findings were consistent across subgroups by age and sex. Sensitivity analyses all supported the robustness of the results and showed good specificity to HM but no other cancers. The main limitation of this observational study is the potential residual confounding effects that could have arisen from the lack of randomization in clozapine or olanzapine use.

Conclusions

Absolute rate difference in HM incidence associated with clozapine is small despite a 2-fold elevated rate. Given the rarity of HM and existing blood monitoring requirements, more restrictive indication for clozapine or special warnings may not be necessary.
Deep learning based predictive modeling to screen natural compounds against TNF-alpha for the potential management of rheumatoid arthritis: Virtual screening to comprehensive in silico investigation
Authors: Nabi Tasnia , Riyed Tanver Hasan , Ornob Akid
Published: December 2024

Rheumatoid arthritis (RA) affects an estimated 0.1% to 2.0% of the world’s population, leading to a substantial impact on global health. The adverse effects and toxicity associated with conventional RA treatment pathways underscore the critical need to seek potential new therapeutic candidates, particularly those of natural sources that can treat the condition with minimal side effects. To address this challenge, this study employed a deep-learning (DL) based approach to conduct a virtual assessment of natural compounds against the Tumor Necrosis Factor-alpha (TNF-α) protein. TNF-α stands out as the primary pro-inflammatory cytokine, crucial in the development of RA. Our predictive model demonstrated appreciable performance, achieving MSE of 0.6, MAPE of 10%, and MAE of 0.5. The model was then deployed to screen a comprehensive set of 2563 natural compounds obtained from the Selleckchem database. Utilizing their predicted bioactivity (pIC50), the top 128 compounds were identified. Among them, 68 compounds were taken for further analysis based on drug-likeness analysis. Subsequently, selected compounds underwent additional evaluation using molecular docking (< − 8.7 kcal/mol) and ADMET resulting in four compounds posing nominal toxicity, which were finally subjected to MD simulation for 200 ns. Later on, the stability of complexes was assessed via analysis encompassing RMSD, RMSF, Rg, H-Bonds, SASA, and Essential Dynamics. Ultimately, based on the total binding free energy estimated using the MM/GBSA method, Imperialine, Veratramine, and Gelsemine are proven to be potential natural inhibitors of TNF-α.
Enamel histomorphometry, growth patterns and developmental trajectories of the first deciduous molar in an Italian early medieval skeletal series
Authors: Magri Stefano , Higgins Owen Alexander , Lugli Federico , Silvestrini Sara , Vazzana Antonino , Bondioli Luca , Nava Alessia , Benazzi Stefano
Published: December 2024

Understanding the growth patterns and developmental trajectories of teeth during early life stages provides valuable insights into the ontogeny of individuals, particularly in archaeological populations where such information is scarce. This study focuses on first deciduous molars, specifically investigating crown formation times and daily secretion rates, through histological analysis. A total of 34 teeth from the Early Medieval necropolises of Casalmoro and Guidizzolo (Mantua, Lombardy, northern Italy) were analysed assessing growth parameters and identifying possible differences between sites and between sexes, which are determined through proteomic analysis. Furthermore, a robust linear regression model relating prism length and secretion time was built to estimate growth rates also in teeth in which the finest incremental markings are not visible. The daily secretion rates (DSR) in inner enamel showed a high homogeneity between dental arches, sexes and the two sites. Values fall within the known range reported in the literature for the same tooth class in archaeological populations. However, a difference in DSR was observed when compared with modern sample published values. Crown formation times and age at crown completion differ between dental arches, with maxillary first molars initiating their matrix apposition earlier than mandibular molars as formerly reported. However, no significant differences were highlighted in association with sex. This study expands our understanding of the growth and development of the first deciduous molars in a medieval population, providing valuable insights into growth trajectories specific to the dental arch. These findings highlight the need for extensive investigations using similar methodologies to attain more accurate and comprehensive information about the developmental patterns of first deciduous molars. Additionally, proteomic analysis improves the capability to conduct sex-specific histological assessments of immature individuals, thanks to this method’s application in determining their sex.
Robust regulation of a PVTOL aircraft subject to crosswind disturbances: Passivity and integral sliding mode approach
Authors: Aguilar-Ibanez Carlos , Suarez-Castanon Miguel S. , Saldivar Belem , Jiménez-Lizárraga Manuel , Rubio de Jesus Jose
Published: December 2024

This paper deals with the problem of robust regulation of a Planar Vertical Takeoff and Landing (PVTOL) aircraft affected by crosswind disturbances. The proposed approach simultaneously exploits the advantages of passivity-based control and the integral sliding mode (ISM) control technique. We demonstrate that the passivity-based controller accomplishes the PVTOL regulation within a guaranteed stability region. At the same time, the ISM controller can effectively counteract the undesirable disturbances effect from the beginning of the operation since the disturbances are never seen in the measurable output. Using the passivity approach with LaSalle’s Invariance Theorem, we construct the required Lyapunov function to establish the closed-loop system stability. The proposed combination of controllers results in a robust system that satisfactorily solves the regulation problem. Numerical simulations are provided to show that the proposed approach allows the tracking of different reference signals: pulse-train shaped trajectory and ellipse-shaped trajectory, considering the presence of perturbations (crosswind). Furthermore, to illustrate the effectiveness of the proposed technique, a comparative analysis considering two robust control strategies is provided.
The use of OpenAlex to produce meaningful bibliometric global overlay maps of science on the individual, institutional, and national levels
Authors: Haunschild Robin , Bornmann Lutz
Published: December 2024

The Social Systems Citations Theory (SSCT) is the most recent theory of citations integrating previous theories. It focuses on communications in science that are formally manifested as publications and citations in scientific communication networks. These networks can be observed and empirically studied by using science maps. Science maps typically visualize networks of communication elements such as key words, cited references, and subject areas. In this study, a procedure to create global overlay maps using OpenAlex is proposed. It is an important advantage of OpenAlex publication and citation data that they are freely available. Overlay maps visualize how the overlaid data (e.g., research of an institution) are positioned in the whole science system (the base map). Six different base maps are provided to the user for their own applications. Using one of these base maps, example overlay maps for two individuals (the authors of this paper) and four research institutions are shown and discussed. A method for normalizing the overlay data is also proposed that can be used for the comparison of two different overlaid units. Overlay maps using raw overlay data display general concepts more pronounced than specific concepts. It is the other way around with their counterparts using normalized overlay data. Advantages and limitations of the proposed overlay approach based on OpenAlex are discussed.
Care home resident identification: A comparison of address matching methods with Natural Language Processing
Authors: Suárez-Paniagua Víctor , Casey Arlene , A. Marwick Charis , K. Burton Jennifer , Callaby Helen , Guthrie Isobel , Guthrie Bruce , Alex Beatrice
Published: December 2024

Background

Care home residents are a highly vulnerable group, but identifying care home residents in routine data is challenging. This study aimed to develop and validate Natural Language Processing (NLP) methods to identify care home residents from primary care address records.

Methods

The proposed system applies an NLP sequential filtering and preprocessing of text, then the calculation of similarity scores between general practice (GP) addresses and care home registered addresses. Performance was evaluated in a diagnostic test study comparing NLP prediction to independent, gold-standard manual identification of care home addresses. The analysis used population data for 771,588 uniquely written addresses for 819,911 people in two NHS Scotland health board regions. The source code is publicly available at https://github.com/vsuarezpaniagua/NLPcarehome.

Results

Care home resident identification by NLP methods overall was better in Fife than in Tayside, and better in the over-65s than in the whole population. Methods with the best performance were Correlation (sensitivity 90.2%, PPV 92.0%) for Fife data and Cosine (sensitivity 90.4%, PPV 93.7%) for Tayside. For people aged ≥65 years, the best methods were Jensen-Shannon (sensitivity 91.5%, PPV 98.7%) for Fife and City Block (sensitivity 94.4%, PPV 98.3%) for Tayside. These results show the feasibility of applying NLP methods to real data concluding that computing address similarities outperforms previous works.

Conclusions

Address-matching techniques using NLP methods can determine with reasonable accuracy if individuals live in a care home based on their GP-registered addresses. The performance of the system exceeds previously reported results such as Postcode matching, Markov score or Phonics score.
Effectiveness of care provided by an itinerant community caregiver in reducing the burden and violence of family caregivers of impaired elderly in Rio de Janeiro, Brazil: A randomized clinical trial
Authors: Lino Valéria Teresa Saraiva , Rodrigues Nadia Cristina Pinheiro , Groisman Daniel , Atie Soraya , Camacho Luiz Antônio Bastos , Perisse Germana
Published: December 2024

Introduction

The aging population and the rise in chronic diseases are linked to a higher number of elderly individuals with impairments. These individuals often depend on family caregivers for basic daily activities, which can impose a significant burden and increase the risk of violence against them.

Objective

To assess the effectiveness of itinerant community caregivers (ICC) in reducing burden, depression and risk of violence among family caregivers of impaired elderly (FCIE), while also increasing their social support.

Methods

Randomized controlled trial with 38 pairs of elderly people and their caregivers. For six months, twice a week, the ICC spent three hours with the elderly, completing tasks given by the FCIE. The primary outcomes were reduction of at least one level in the burden, and or in the risk of violence against the elderly. The secondary outcomes were a decrease in depressive symptoms and/or an increase in social support. Multiple log binomial regression models were used to assess the relationship between the predictors and the response variables.

Results

In the FCIE group, most individuals providing care were women who spent over 16 hours each day in the task of caring for the impaired elderly, with most falling between the ages of 41 and 60. Over half of them were children of the elderly participants. In the intervention group, there was a significant decrease in the likelihood of violence against the elderly, with a 10-fold reduction. However, other endpoints did not present significant changes.

Conclusion

The involvement of an ICC in the care of impaired elderly can contribute to reducing domestic violence by FCIE.
Management of possible serious bacterial infections in young infants where referral is not possible in the context of existing health system structure in Mbeya, Tanzania: Experience and lessons from the end line assessment
Authors: Ngadaya Esther , Manu Alexander , Mmweteni Mary , Burengelo Dorica , Philbert Doreen , Kagaruki Gibson , Isangula Kahabi , Senkoro Mbazi , Kimaro Godfather , Kahwa Amos , Mazige Fikiri , Bundala Felix , Iriya Nemes , Donard Francis , Kitinya Caritas , Minja Victor , Nyakairo Festo , Gupta Gagan , Pearson Luwei , Kim Minjoon , Mfinanga Sayoki , Baker Ulrika , Hailegebriel Tedbabe Degefie
Published: December 2024

Severe bacterial infections (SBIs) are a leading cause of neonatal deaths in low- and middle-income countries. World Health Organization’s (WHO’s) guideline for outpatient management of danger signs indicating possible serious bacterial infections (PSBI) when referral is not possible was adopted by three pilot district councils in Mbeya Region, in Tanzania (Busekelo, Kyela and Mbarali Districts) in 2018 (the PSBI project). This study documented changes in practice during the PSBI project, and lessons learned. A cross-sectional study was conducted using both qualitative and quantitative data collection methods between July 2021 and January 2022, post-implementation. The study participants comprised stakeholders, health workers, community health workers, and mothers/fathers/caregivers who had a young infant with PSBI. Study tools included record review, quantitative, in-depth, and key informant interviews. Quantitative data were analysed using STATA version 15 (STATACorp Inc., TX, USA), whereas qualitative data were analysed using a framework analysis approach. Our assessment showed that 2,228 young infants (0–59 days old) from the three districts were classified as having PSBI. The majority, 1,607 (72.1%) had fast breathing as the only danger sign, while 621 (27.9%) were classified as having severe illness. All 621 young infants with severe illness were counselled and offered referral to a higher-level health facility; however, only 174 of them (28%) accepted the referral. The remaining 447 severely ill infants, for whom referral was not possible, were treated at the primary health facilities with gentamicin injection and amoxicillin dispersible tablets (DT). When referral is not feasible, outpatient treatment for young infants with signs of PSBI is possible within existing health system in Tanzania, based on experience after this pilot project. However, successful scale-up of outpatient management for PSBI will require commitments from government and key stakeholders to strengthen healthcare systems.