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This paper explores the theory of ‘Thoughtful Intelligence’. This theory proposes that the capacity to realize the impact of one’s statements and actions on the continued existence, dignity, and development of other people and nations is ‘Thoughtful Intelligence’. I show that the 4 unique thoughtful features (self point of reference, human point of reference, nature point of reference, and creator point of reference) result in a ‘Thoughtful’ leadership role. Applying this to climate change management enables one to characterize and visualize the forthcoming flow of Thoughtful Intelligence. A Delphi-focused method helped identify 7 dynamics of thoughtful climate statesmanship, including carbon neutrality, offsetting carbon in neighboring countries, fighting climate change, integrity of social well-being, preserving environment and culture, caring use of limited resources, and gross national happiness. A Delphi-exploratory method was used to clarify thoughtful climate statesmanship. The consensual 95% results documented that the best thoughtful climate statesmanship belonged to Bhutan. The documentation of thoughtful climate statesmanship is strengthening the literature on statesmanship. Summit leaders, scientists, and people in business globally can benefit from this study.

A higher rate of consanguineous marriages is associated with the increasing prevalence of genetic disorders, imposing a significant burden on families, public health, and healthcare systems. Genetic testing facilitates the earlier detection of disease and personalized treatment approaches. Therefore, this study aims to assess knowledge, awareness, attitudes, and concerns regarding genetic testing in the Pakistani population. Participants (n = 494) were asked about factors that influence attitudes toward undergoing genetic testing. Furthermore, the study also investigates the concerns and reservations held by the Pakistani population regarding genetic testing. Participants indicated that consanguineous marriages lead to an increased risk of hereditary disorders and agreed that knowledge of genetic diseases can improve the quality of life. Almost 80% of the respondents know the term, and the majority of them know about genetic testing. 87.7% of respondents agreed to genetic screening before marriage, and 39.9% were willing to undergo genetic testing. More knowledge was significantly associated with a higher likelihood of accepting genetic testing, indicating potential acceptance if integrated into standard procedures. Those with a family history of genetic disorders were more positive in accepting genetic testing. The level of understanding regarding genetic testing also influences the concerns. Cultural or religious beliefs may also affect the decision to accept genetic testing. The survey reveals diverse opinions and knowledge levels regarding genetic testing in Pakistan. While there was generally positive interest, concerns about privacy, accuracy, and cultural factors should be addressed. Education and awareness campaigns could help improve understanding and acceptance., Competing Interests: Declarations. Ethical approval: This article does not contain any studies of human or animal subjects performed by the any of the authors. Informed consent was obtained from all participants for being included in the study. Ethical publication statement. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease that can be easily missed due to its variable presentation. Acquired angioedema (AAE) is a rare first presentation of SLE. We report a case of a 23-year-old woman who presented to the emergency department with rapidly progressive swelling of the tongue and neck, followed by respiratory discomfort and a generalized non-itchy rash. A tracheostomy was performed to relieve her symptoms. Her history, examination, and relevant investigations all indicated SLE. She was treated with high-dose steroids, and pulse therapy with methylprednisolone was given for three days. Hydroxychloroquine was added, but she developed sepsis and an acute flare of SLE secondary to tracheostomy site infection. Subsequently, she was treated with broad-spectrum antibiotics, followed by a tapering dose of steroids and a maintenance dose of azathioprine. She responded to treatment, tracheostomy reversal was performed, and the patient was discharged., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Ethical Committee of Abbas Institute of Medical Sciences (AIMS) issued approval ERB No.: 1451. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Parvaiz Rasheed et al.)

Introduction: Patients with diabetes require healthcare and information that are accurate and extensive. Large language models (LLMs) like ChatGPT herald the capacity to provide such exhaustive data. To determine (a) the comprehensiveness of ChatGPT's responses in Urdu to diabetes-related questions and (b) the accuracy of ChatGPT's Urdu responses when compared to its English responses., Methods: A cross-sectional observational study was conducted. Two reviewers experienced in internal medicine and endocrinology graded 53 Urdu and English responses on diabetes knowledge, lifestyle, and prevention. A senior reviewer resolved discrepancies. Responses were assessed for comprehension and accuracy, then compared to English., Results: Among the Urdu responses generated, only two of 53 (3.8%) questions were graded as comprehensive, and five of 53 (9.4%) were graded as correct but inadequate. We found that 25 of 53 (47.2%) questions were graded as mixed with correct and incorrect/outdated data, the most significant proportion of responses being graded as such. When considering the comparison of response scale grading the comparative accuracy of Urdu and English responses, no Urdu response (0.0%) was considered to have more accuracy than English. Most of the Urdu responses were found to have an accuracy less than that of English, an overwhelming majority of 49 of 53 (92.5%) responses., Conclusion: We found that although the ability to retrieve such information about diabetes is impressive, it can merely be used as an adjunct instead of a solitary source of information. Further work must be done to optimize Urdu responses in medical contexts to approximate the boundless potential it heralds., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Cadmium (Cd) toxicity significantly threatens agricultural productivity and food safety. Developing effective strategies to enhance plant tolerance to Cd stress is essential. This study investigates the synergistic effects of biochar (BC) and gibberellic acid (GA3) on mitigating Cd toxicity in maize (Zea mays), focusing on their impact on oxidative stress markers and antioxidant enzyme activities. Soil samples were collected from the Cholistan Institute of Desert Studies (CIDS) and analyzed for trace metal ions and other properties. Biochar was produced from fruit and vegetable waste, washed, washed, deashed, and mixed with 10 ppm GA3. FH-1036 hybrid maize seeds were sterilized and planted in pots containing soil with varying Cd levels (0, 8, and 16 mg Cd/kg soil). Twelve treatments were established, including control, GA3, BC, and their combinations under different Cd stress levels. Plants were irrigated to maintain 60% field capacity and harvested at the V10 growth stage. Hydrogen peroxide (H 2 O 2 ) contents and activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) were measured in roots, stems, and leaves. Statistical analysis was performed using OriginPro 2021, with ANOVA and Fisher's LSD test used to determine significant differences. GA3 and BC treatments significantly reduced H 2 O 2 levels in maize roots, stems and leaves under Cd stress. The combined treatment of GA3 + BC showed the most significant reduction in H 2 O 2 levels across all plant parts, reducing root H 2 O 2 by 50%, stem H 2 O 2 by 55%, and leaf H 2 O 2 by 53% under severe Cd stress (16 mg Cd/kg). SOD activity increased under non-stress conditions but decreased under Cd stress, with the highest activity observed in the combined treatment. POD activity followed a similar pattern, with GA3 + BC treatment resulting in the most significant increases under non-stress conditions and the least reductions under Cd stress. CAT activity showed substantial increases with GA3 + BC treatment, particularly under severe Cd stress, with a notable rise over the control. APX activity also exhibited enhancements with GA3 and BC treatments, especially in the combined treatment under various Cd stress levels. This study highlights the potential of combined BC and GA3 treatments in improving Cd stress tolerance in maize. Future research should focus on field trials and the long-term impacts of these treatments on crop productivity and soil health., (© 2024. The Author(s).)

Objective: To evaluate the effectiveness, cost-effectiveness and feasibility of internet-based Cognitive Behavioural Therapy (CBT) in the treatment of body dysmorphic disorder., Methods: The systematic review was conducted from August 19 to September 22, 2023, and comprised search on Cochrane Library, Embase, Google Scholar, PubMed, PsycINFO and Web of Science databases using specific key words for studies published in the English language from 2010 onwards. Grey literature and pertinent conference proceedings were also searched to include as many studies as possible that investigated internet-based cognitive behavioural therapy in the treatment of body dysmorphic disorder. Data extraction was done, and the selected studies were subjected to quality assessment, followed by a narrative synthesis of the findings., Results: Out of the 6,837 studies initially identified, 8(0.11%) were analysed in detail. Of the 8 studies, 4(50%) were RCTs, while 5(62.5%) had been conducted in Sweden. Therapist-guided internet-based cognitive behavioural therapy interventions consistently demonstrated efficacy with respect to reducing body dysmorphic disorder symptom severity, improving insight, and enhancing quality of life. Cost-effectiveness analyses highlighted the favourable economic aspect of internet-based cognitive behavioural therapy. Feasibility and acceptability were demonstrated by high participant engagement and satisfaction., Conclusion: Internet-based cognitive behavioural therapy showed promise in addressing the treatment gap in body dysmorphic disorder care, offering accessible, cost-effective and feasible interventions.

Immunofluorescence microscopy is extensively used in characterization of trophoblast differentiation in vitro. However, such data is primarily used to confirm the presence of protein markers or qualitatively compare levels of protein markers across experimental conditions. Imaging data, when processed and analyzed appropriately can provide quantitative and spatial information, and provide biological insight. Towards this end, here we present MATroph, an open-source MATLAB-based computational tool to process images generated by immunofluorescent microscopy. MATroph automatically executes a series of image processing operations, including the classification of red, blue, and green channels from images, background extraction, morphological operations, and image filtering. From the isolated blue channels corresponding to nuclear staining, this tool generates numerical values for cell number. Additionally, relative levels and spatial location of proteins are obtained by mapping red and green channel pixels to blue pixels by assigning minimum pixel distance between the blue and other color objects. Thus, this tool provides information about intracellular protein accumulation areas. Additionally, this tool can also classify cells as single cells or part of colonies, and extract information on protein levels for each; this is particularly useful for quantitative studies on extravillous trophoblast maturation. We provide a user-guide to analyze the relative levels of markers relevant to human trophoblast stem cell self-renewal and differentiation. Importantly, MATroph is composed of a simple MATLAB algorithm, and its implementation requires minimal expertise in programming., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Distance-based topological indices are numerical parameters that are derived from the distances between atoms in a molecular structure, and they provide a quantitative measure of the topology and geometry of a molecule. The distance-based topological indices uses to predict various properties of molecules, including their boiling points, melting points, and solubility. It also predicts the biological activity of molecules, including their pharmacological and toxicological properties. Pentagonal chain molecules are organic compounds that consist of a linear chain of five-membered (pentagons) connected by carbon and bonds. These molecules have unique structural and electronic properties that make them useful in a variety of applications. Motivated by the pentagonal chain molecules, we have considered a pentagonal chain graph and it is denoted by Pn. We have computed some distance based topological indices for Pn. The paper focuses on a pentagonal chain molecules denoted by G, and derives several distance-based topological indices. These indices compromise insights into physicochemical properties, aid in identifying structural characterizations, and enhance understanding of molecular properties., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Human trophoblast stem cells (hTSCs) have emerged as a powerful tool for modeling the placental cytotrophoblast (CTB) in vitro. hTSCs were originally derived from CTBs of the first trimester placenta or blastocyst-stage embryos in trophoblast stem cell medium (TSCM) that contains epidermal growth factor (EGF), the glycogen synthase kinase-beta (GSK3β) inhibitor CHIR99021, the transforming growth factor-beta (TGFβ) inhibitors A83-01 and SB431542, valproic acid (VPA), and the Rho-associated protein kinase (ROCK) inhibitor Y-27632. Here we show that hTSCs can be derived from CTBs isolated from the term placenta, using TSCM supplemented with a low concentration of mitochondrial pyruvate uptake inhibitor UK5099 and lipid-rich albumin (TUA medium). Notably, hTSCs could not be derived from term CTBs using TSCM alone, or in the absence of either UK5099 or lipid-rich albumin. Strikingly, hTSCs cultured in TUA medium for a few passages could be transitioned into TSCM and cultured thereafter in TSCM. hTSCs from term CTBs cultured in TUA medium as well as those transitioned into and cultured in TSCM thereafter could be differentiated to the extravillous trophoblast and syncytiotrophoblast lineages and exhibited high transcriptome similarity with hTSCs derived from first trimester CTBs. We anticipate that these results will enable facile derivation of hTSCs from normal and pathological placentas at birth with diverse genetic backgrounds and facilitate in vitro mechanistic studies in trophoblast biology.

Cadmium (Cd), being a heavy metal, tends to accumulate in soils primarily through industrial activities, agricultural practices, and atmospheric deposition. Maize, being a staple crop for many regions, is particularly vulnerable to Cd contamination, leading to compromised growth, reduced yields, and potential health risks for consumers. Biochar (BC), a carbon-rich material derived from the pyrolysis of organic matter has been shown to improve soil structure, nutrient retention and microbial activity. The choice of biochar as an ameliorative agent stems from its well-documented capacity to enhance soil quality and mitigate heavy metal stress. The study aims to contribute to the understanding of the efficacy of biochar in combination with GA 3 , a plant growth regulator known for its role in promoting various physiological processes, in mitigating the adverse effects of Cd stress. The detailed investigation into morpho-physiological attributes and biochemical responses under controlled laboratory conditions provides valuable insights into the potential benefits of these interventions. The experimental design consisted of three replicates in a complete randomized design (CRD), wherein soil, each containing 10 kg was subjected to varying concentrations of cadmium (0, 8 and 16 mg/kg) and biochar (0.75% w/w base). Twelve different treatment combinations were applied, involving the cultivation of 36 maize plants in soil contaminated with Cd (T1: Control (No Cd stress; T2: Mild Cd stress (8 mg Cd/kg soil); T3: Severe Cd stress (16 mg Cd/kg soil); T4: 10 ppm GA 3 (No Cd stress); T5: 10 ppm GA 3  + Mild Cd stress; T6: 10 ppm GA 3  + Severe Cd stress; T7: 0.75% Biochar (No Cd stress); T8: 0.75% Biochar + Mild Cd stress; T9: 0.75% Biochar + Severe Cd stress; T10: 10 ppm GA 3  + 0.75% Biochar (No Cd stress); T11: 10 ppm GA 3  + 0.75% Biochar + Mild Cd stress; T12: 10 ppm GA3 + 0.75% Biochar + Severe Cd stress). The combined application of GA 3 and BC significantly enhanced multiple parameters including germination (27.83%), root length (59.53%), shoot length (20.49%), leaf protein (121.53%), root protein (99.93%), shoot protein (33.65%), leaf phenolics (47.90%), root phenolics (25.82%), shoot phenolics (25.85%), leaf chlorophyll a (57.03%), leaf chlorophyll b (23.19%), total chlorophyll (43.77%), leaf malondialdehyde (125.07%), root malondialdehyde (78.03%) and shoot malondialdehyde (131.16%) across various Cd levels compared to the control group. The synergistic effect of GA 3 and BC manifested in optimal leaf protein and malondialdehyde levels indicating induced tolerance and mitigation of Cd detrimental impact on plant growth. The enriched soils showed resistance to heavy metal toxicity emphasizing the potential of BC and GA 3 as viable strategy for enhancing maize growth. The application of biochar and gibberellic acid emerges as an effective means to mitigate cadmium-induced stress in maize, presenting a promising avenue for sustainable agricultural practices., (© 2024. The Author(s).)

Over the course of the COVID-19 pandemic, several SARS-CoV-2 variants have emerged that may exhibit different etiological effects such as enhanced transmissibility and infectivity. However, genetic variations that reduce virulence and deteriorate viral fitness have not yet been thoroughly investigated. The present study sought to evaluate the effects of viral genetic makeup on COVID-19 epidemiology in Pakistan, where the infectivity and mortality rate was comparatively lower than other countries during the first pandemic wave. For this purpose, we focused on the comparative analyses of 7096 amino-acid long polyprotein pp1ab. Comparative sequence analysis of 203 SARS-CoV-2 genomes, sampled from Pakistan during the first wave of the pandemic revealed 179 amino acid substitutions in pp1ab. Within this set, 38 substitutions were identified within the Nsp3 region of the pp1ab polyprotein. Structural and biophysical analysis of proteins revealed that amino acid variations within Nsp3's macrodomains induced conformational changes and modified protein-ligand interactions, consequently diminishing the virulence and fitness of SARS-CoV-2. Additionally, the epistatic effects resulting from evolutionary substitutions in SARS-CoV-2 proteins may have unnoticed implications for reducing disease burden. In light of these findings, further characterization of such deleterious SARS-CoV-2 mutations will not only aid in identifying potential therapeutic targets but will also provide a roadmap for maintaining vigilance against the genetic variability of diverse SARS-CoV-2 strains circulating globally. Furthermore, these insights empower us to more effectively manage and respond to potential viral-based pandemic outbreaks of a similar nature in the future., (© 2024. The Author(s).)

Ionic liquids (ILs) are a class of liquid salts with characteristics such as a low melting point, an ionic nature, non-volatility, and tunable properties. Because of their adaptability, they have a significant influence in the field of fluorescence. This paper reviews the primary literature on the use of ILs in fluorescence sensing technologies. The kind of target material is utilized to classify the fluorescence sensors made with the use of ILs. They include using ILs as probes for metals, nitro explosives, small organic compounds, anions, and gases. The efficacy of an IL-based fluorescence sensor depends on the precise design to guarantee specificity, sensitivity, and a consistent reaction to the desired analyte. The precise method can differ depending on the chemical properties of the IL, the choice of fluorophore, and the interactions with the analyte. Overall, the viability of the aforementioned materials for chemical analysis is evaluated, and prospective possibilities for further development are identified., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Monkeypox (Mpox) is a zoonotic viral disease caused by the monkeypox virus (MPXV), a member of the Orthopoxvirus genus. The recent occurrence of Mpox infections has become a significant global issue in recent months. Despite being an old disease with a low mortality rate, the ongoing multicountry outbreak is atypical due to its occurrence in nonendemic countries. The current review encompasses a comprehensive analysis of the literature pertaining to MPXV, with the aim of consolidating the existing data on the virus's epidemiological, biological, and clinical characteristics, as well as vaccination and treatment regimens against the virus., (© 2023 Wiley-VCH GmbH.)

Multiple studies in the literature have demonstrated that synthetic compounds containing heterocyclic rings possess a reparative potential against acute and chronic inflammation. In the present study, two novel thiosemicarbazone derivatives based on l-ethyl-6-(thiophen-2-yl)indoline-2,3-dione with different phenyl substituted thiosemicarbazides were synthesized by condensation reaction and the structures of proposed target compounds (KP-2 and KP-5) were confirmed by UV-VIS, FTIR, 1 H-NMR and 13 C-NMR. In-vitro anti-inflammatory behavior of KP-2 and KP-5 was confirmed by bovine serum albumin (BSA) and ovine serum albumin (OSA) analysis. Acute and chronic anti-inflammatory potential of synthesized compounds were evaluated by using carrageenan and complete Freund's adjuvant (CFA) as inflammation-inducing agents, respectively. Inhibition of pro-inflammatory mediators and prevention of protein denaturation owing to synchronization of more electronegative flouro-groups substituted on phenyl rings along with heterocyclic indoline ring provides anti-inflammatory effects and are corroborated by radiological, histopathological analysis. Additional support was provided through density functional theory (DFT) and molecular docking. KP-5 exhibited excellent lead-likeness based on its physicochemical parameters, making it a viable drug candidate. The synthesized compounds also showed promising ADMET properties, enhancing their potential as therapeutic agents. These findings emphasize the pivotal role of new compounds for drug design and development., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The LiNi 0.8 Mn 0.1 Co 0.1 O 2 (NMC811) cathode material has been of significant consideration owing to its high energy density for Li-ion batteries. However, the poor cycling stability in a carbonate electrolyte limits its further development. In this work, we report the excellent electrochemical performance of the NMC811 cathode using a rational electrolyte based on organic ionic plastic crystal N -ethyl- N -methyl pyrrolidinium bis(fluorosulfonyl)imide C 2 mpyr[FSI], with the addition of (1:1 mol) LiFSI salt. This plastic crystal electrolyte (PC) is a thick viscous liquid with an ionic conductivity of 2.3 × 10 -3 S cm -1 and a high Li + transference number of 0.4 at ambient temperature. The NMC811@PC cathode delivers a discharge capacity of 188 mA h g -1 at a rate of 0.2 C with a capacity retention of 94.5% after 200 cycles, much higher than that of using a carbonate electrolyte (54.3%). Moreover, the NMC811@PC cathode also exhibits a superior high-rate capability with a discharge capacity of 111.0 mA h g -1 at the 10 C rate. The significantly improved cycle performance of the NMC811@PC cathode can be attributed to the high Li + conductivity of the PC electrolyte, the stable Li + conductive CEI film, and the maintaining of particle integrity during long-term cycling. The admirable electrochemical performance of the NMC811|C 2 mpyr[FSI]:[LiFSI] system exhibits a promising application of the plastic crystal electrolyte for high voltage layered oxide cathode materials in advanced lithium-ion batteries.

Several emerging therapies kill cancer cells primarily by inducing necrosis. As necrosis activates immune cells, potentially, uncovering the molecular drivers of anticancer therapy-induced necrosis could reveal approaches for enhancing immunotherapy efficacy. To identify necrosis-associated genes, we performed a genome-wide CRISPR-Cas9 screen with negative selection against necrosis-inducing preclinical agents BHPI and conducted follow-on experiments with ErSO. The screen identified transient receptor potential melastatin member 4 (TRPM4), a calcium-activated, ATP-inhibited, sodium-selective plasma membrane channel. Cancer cells selected for resistance to BHPI and ErSO exhibited robust TRPM4 downregulation, and TRPM4 reexpression restored sensitivity to ErSO. Notably, TRPM4 knockout (TKO) abolished ErSO-induced regression of breast tumors in mice. Supporting a broad role for TRPM4 in necrosis, knockout of TRPM4 reversed cell death induced by four additional diverse necrosis-inducing cancer therapies. ErSO induced anticipatory unfolded protein response (a-UPR) hyperactivation, long-term necrotic cell death, and release of damage-associated molecular patterns that activated macrophages and increased monocyte migration, all of which was abolished by TKO. Furthermore, loss of TRPM4 suppressed the ErSO-induced increase in cell volume and depletion of ATP. These data suggest that ErSO triggers initial activation of the a-UPR but that it is TRPM4-mediated sodium influx and cell swelling, resulting in osmotic stress, which sustains and propagates lethal a-UPR hyperactivation. Thus, TRPM4 plays a pivotal role in sustaining lethal a-UPR hyperactivation that mediates the anticancer activity of diverse necrosis-inducing therapies., Significance: A genome-wide CRISPR screen reveals a pivotal role for TRPM4 in cell death and immune activation following treatment with diverse necrosis-inducing anticancer therapies, which could facilitate development of necrosis-based cancer immunotherapies., (©2023 American Association for Cancer Research.)

Background: Asthma attacks are a common and important problem. Someone experiences an asthma attack in the United Kingdom every 10 seconds. Asthma attacks cause coughing, wheezing, breathlessness, and chest tightness and are highly stressful for patients. They result in reduced quality of life, with days lost from work or school. Asthma attacks are treated with oral corticosteroids (OCSs), but these have many short- and long-term side effects. Asthma monoclonal antibodies (mAbs) have revolutionized the treatment of severe asthma by reducing asthma attacks and OCS burden by over 50%, but some people still experience attacks while on mAbs. The MEX study showed that residual asthma attacks are broadly eosinophilic (high fractional exhaled nitric oxide [FeNO]) or noneosinophilic (low FeNO), but it did not measure response to OCS treatment. There is an evidence gap in understanding the clinical and inflammatory responses that occur when using OCSs to treat residual asthma attacks in patients taking asthma mAbs., Objective: The primary objective is to compare the clinical recovery between high-FeNO and low-FeNO attacks after acute treatment with oral prednisolone among people established on long-term asthma mAb treatment. The exploratory objective is to compare the inflammatory response to acute treatment with oral prednisolone between high-FeNO and low-FeNO attacks., Methods: BOOST (Breakthrough Asthma Attacks Treated With Oral Steroids) is a single-center, prospective observational study of 60 adults established on long-term asthma mAb treatment who receive acute treatment with oral prednisolone (usual care) for an asthma attack. The primary outcome will be the proportion of treatment failure (the need to start oral prednisolone or antibiotics or an unscheduled health care visit for asthma, following an attack) at day 28. The secondary outcomes will be the change in forced expiratory volume in 1 second and the change in visual analogue scale symptom score between the stable state, attack, day 7, and day 28 visits. The exploratory outcomes include the changes in sputum, nasal, and blood inflammometry between the stable state, attack, day 7, and day 28 visits., Results: The last asthma attack visit is anticipated to occur in December 2023. Data analysis and publication will take place in 2024., Conclusions: We will test the hypothesis that there is a difference in the rate of recovery of clinical and inflammatory measures between high-FeNO and low-FeNO asthma attacks that occur in patients on mAb therapy. The study data will help power a future randomized placebo-controlled trial of prednisolone treatment for nonsevere attacks in patients treated with asthma mAbs and will provide important information on whether corticosteroid treatment should be FeNO-directed., International Registered Report Identifier (irrid): DERR1-10.2196/46741., (©Imran Howell, Mahdi Mahdi, Mona Bafadhel, Timothy S C Hinks, Sanjay Ramakrishnan, James Melhorn, Maisha Jabeen, Ian D Pavord. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 23.06.2023.)

Thalassemia syndromes are a group of autosomal, recessively inherited, single-gene hemoglobinopathies with varied mucocutaneous manifestations. There is, however, a scarcity of these findings in the literature. This descriptive observational cross-sectional study was conducted to describe mucocutaneous manifestations in multi-transfused beta-thalassemia major children. The study comprised 68 thalassemia major children attending the thalassemia unit for blood transfusion at a tertiary care hospital in North India. A dermatologist conducted a detailed examination to look into the presence of any mucocutaneous manifestations, including disorders of the hair and nails. The age range of enrolled thalassemic children was 6 months-19 years, with an average age of 10.5 years; the boy versus girl ratio was 1.72:1. All enrolled children had at least one cutaneous manifestation. Common dermatologic manifestations observed in these patients included hyperpigmentation of the knuckles (60.2%), moderate pallor (42.6%), icterus (26.4%), lusterless hair (20.5%), leukonychia striata or horizontal white streaks on the nails (14.7%), and oral ulcers (10.2%). A careful evaluation of mucocutaneous manifestations, including disorders of the hair and nails, is required in multi-transfused thalassemic children to provide an early diagnosis of dermatologic manifestations.

Human trophoblast stem cells (hTSCs) have emerged as a powerful tool to model early placental development in vitro. Analogous to the epithelial cytotrophoblast in the placenta, hTSCs can differentiate into cells of the extravillous trophoblast (EVT) lineage or the multinucleate syncytiotrophoblast (STB). Here we present a chemically defined culture system for STB and EVT differentiation of hTSCs. Notably, in contrast to current approaches, we neither utilize forskolin for STB formation nor transforming growth factor-beta (TGFβ) inhibitors or a passage step for EVT differentiation. Strikingly, the presence of a single additional extracellular cue-laminin-111-switched the terminal differentiation of hTSCs from STB to the EVT lineage under these conditions. In the absence of laminin-111, STB formation occurred, with cell fusion comparable to that obtained with differentiation mediated by forskolin; however, in the presence of laminin-111, hTSCs differentiated to the EVT lineage. Protein expression of nuclear hypoxia-inducible factors (HIF1α and HIF2α) was upregulated during EVT differentiation mediated by laminin-111 exposure. A heterogeneous mixture of Notch1 + EVTs in colonies and HLA-G + single-cell EVTs were obtained without a passage step, reminiscent of heterogeneity in vivo. Further analysis showed that inhibition of TGFβ signaling affected both STB and EVT differentiation mediated by laminin-111 exposure. TGFβ inhibition during EVT differentiation resulted in decreased HLA-G expression and increased Notch1 expression. On the other hand, TGFβ inhibition prevented STB formation. The chemically defined culture system for hTSC differentiation established herein facilitates quantitative analysis of heterogeneity that arises during hTSC differentiation and will enable mechanistic studies in vitro., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The transmission of pathogens through contact with contaminated surfaces is an important route for the spread of infections. The recent outbreak of COVID-19 highlights the necessity to attenuate surface-mediated transmission. Currently, the disinfection and sanitization of surfaces are commonly performed in this regard. However, there are some disadvantages associated with these practices, including the development of antibiotic resistance, viral mutation, etc.; hence, a better strategy is necessary. In recent years, peptides have been studied to be utilized as a potential alternative. They are part of the host immune defense and have many potential in vivo applications in drug delivery, diagnostics, immunomodulation, etc. Additionally, the ability of peptides to interact with different molecules and membrane surfaces of microorganisms has made it possible to exploit them in ex vivo applications such as antimicrobial (antibacterial and antiviral) coatings. Although antibacterial peptide coatings have been studied extensively and proven to be effective, antiviral coatings are a more recent development. Therefore, this study aims to highlight antiviral coating strategies and the current practices and application of antiviral coating materials in personal protective equipment, healthcare devices, and textiles and surfaces in public settings. Here, we have presented a review on potential techniques to incorporate peptides in current surface coating strategies that will serve as a guide for developing cost-effective, sustainable and coherent antiviral surface coatings. We further our discussion to highlight some challenges of using peptides as a surface coating material and to examine future perspectives., Competing Interests: The authors declare no conflict of interest.