bluuebunny/crossref_metadata_2025 huggingface dataset:
Haematological, Clinical and Radiological Prognostic Markers in Young COVID19 Patients during the Second Wave: A Prospective Cohort Study
Authors: Pandey Ankit , Bargunam Priyadharshini , Goveas Christina , Sridhara S
Published: December 2023

Introduction: The devastating outbreak of the second wave of Coronavirus Disease-2019 (COVID-19), resulting in numerous deaths among young individuals, has been the deadliest pandemic witnessed in this century. It caught us off guard by affecting young people and those without any underlying health conditions, leaving profound psychological and economic scars. Aim: To investigate various prognostic markers (haematological and clinicoradiological) in young COVID-19 patients during the second wave. Materials and Methods: This prospective, cohort study was conducted at a tertiary care centre in Karnataka, India from May 1st, 2021, to June 30th, 2021. All COVID-19 patients between the ages of 18 and 45, regardless of their pre-existing health status, who tested positive on Real-time Reverse TranscriptasePolymerase Chain Reaction (RT-PCR)/Rapid Antigen Test (RAT) or showed typical Computed Tomography (CT) changes, were included. Patients with COVID-19 symptoms but negative RT-PCR/RAT results and without typical CT changes were excluded. Clinical, haematological, and radiological parameters were compared between the survivor group and non survivor group, and the results were analysed using measures of central tendency (mean, median, and mode), Chi-square test, and Independent t-test Statistical Package for Social Sciences (SPSS) version 21.0. Results: A total of 624 cases aged between 18 and 45 were included in the study. Among them, 481 (77.08%) patients survived, while 143 (22.92%) patients were dead. Of the 624 cases, 376 (60.26%) were males, 247 (39.58%) were females, and 1 (0.16%) was transgender. Factors associated with increased mortality included older age (>40 years), presentation with cough (119 patients, 83.2%) and dyspnoea (120 patients, 83.9%), asthma (7 patients, 1.1%), clinical classification based on respiratory rate, oxygen saturation, CT changes, and requirement for mechanical ventilation (78 patients, 54.5% in the Severe category and 54 patients, 37.8% in the Critical category), increased white blood cell count (mean μ=9685.8±5470.9), increased neutrophils (μ=8216±4986.9), elevated levels of CRP (μ=96.7±65.84 mg/dL), serum ferritin (μ=571.4±353.15 ng/ mL), LDH (μ=1268.7±835 U/L), D-dimer (μ=74.87±527), serum globulin, ALT (μ=67.6±58.5 U/L), AST (μ=76.4±62 U/L), ALP (μ=120±89 U/L), urea, creatinine, decreased levels of albumin, total protein, haemoglobin, and lymphopenia (μ=1096.1±795.9). Additionally, a CT score >15 was associated with increased mortality. Conclusion: The aforementioned clinical, haematological, and radiological predictive biomarkers were associated with poor outcomes in young COVID-19 patients. Therefore, prompt and intensive management should be implemented to improve the prognosis of these patients.
An Innovative Laboratory Technique Showcasing the Synergy among CeftazidimeAvibactam and Aztreonam in Combating Infections caused by Enterobacterales producing Metallo-beta-lactamases: A Prospective Study
Authors: Ghogale Shital Shrikant , Pathak Ketaki Niranjan
Published: December 2023

ntroduction: Combination therapy with CeftazidimeAvibactam (CAZ-AVI) and Aztreonam (ATM) has been studied in the context of infections caused by Enterobacterales that produce Metallo-Beta-Lactamases (MBL). The development of combination therapy is a crucial factor in combating MBLproducing Enterobacterales. As most isolates from Intensive Care Unit (ICU) patients produce a variety of beta-lactamases, offering resistance to a broad range of antibiotics, they need to be treated with the CAZ-AVI and ATM combination. This study addresses a pressing public health issue-the rise of multidrugresistant bacteria, particularly MBL-producing Enterobacterales. By investigating the synergy between CAZ-AVI and ATM, the study aims to provide valuable insights to guide clinical practice, improve patient outcomes, and contribute to the global effort to combat antibiotic resistance. Aim: To demonstrate the synergy between CAZ-AVI and ATM in patients with infections caused by MBL-producing Enterobacterales. Materials and Methods: A prospective study was conducted in the Department of Microbiology at Symbiosis Medical College for Women (SMCW) and Symbiosis University Hospital and Research Centre (SUHRC), Symbiosis International (Deemed University), Lavale, Pune, Maharashtra, India. The study duration was six months, from January 2023 to June 2023. All isolates meeting the inclusion criteria were processed to demonstrate synergy between CAZ-AVI and ATM. Isolates from the Enterobacteriaceae family with resistant breakpoints for carbapenemase, ceftazidimeavibactam, and aztreonem, as determined by the Phoenix automated system, were included in the study. Restoration of the ATM breakpoint was observed following the addition of CAZ/AVI to ATM. Breakpoints provided by the BD Phoenix system were compared to the results obtained from CAZ/AVI and ATM disc diffusion/stacking, E-strip/disc methods, in terms of susceptibility and resistance. Results were simultaneously compared with the broth disc elution test, considered the gold standard. Results: Sensitivity, specificity, Positive Predictive Value (PPV), and Negative Predictive Value (NPV) were calculated for the E-test/disc and disc stacking methods. The disc stacking synergy test demonstrated a PPV of 96.88% and an NPV of 62.5%. By using the E-test/disc, the ATM/CAZ-AV synergy test revealed a PPV of 97.22% and an NPV of 83.33% when CAZ/ AVI was added to ATM. Comparatively, disc stacking was less sensitive than the broth disc elution. Conclusion: In the majority of MBL-producing Enterobacterales that are ATM-resistant, the CAZ/AVI+ATM combination showed strong synergy. In the microbiology laboratory, the E-test/disc and disc stacking approaches are rapid, repeatable, and reliable methods for checking clinically significant synergy.
Hemiagenesis of the Thyroid in a Seven-year-old Child: A Case Report
Authors: Ramteke Anshuta Abhijit , Maldhure Swati , Dhawan Vaishali
Published: December 2023

Thyroid Hemiagenesis (TH) is a rare condition characterised by developmental abnormalities of the thyroid, often observed on the left-side, with a higher prevalence in females. It is commonly associated with a lack of the isthmus. A seven-year-old boy presented to the Ear Nose Throat (ENT) Department with chief complaints of bilateral ear block sensation and dull aching earache persisting for two months, for which syringing was performed. No family history of TH or any past surgeries related to the neck, thyroid, or parathyroid were reported. In recent laboratory tests, his Thyroid Stimulating Hormone (TSH) level was 7.23 μIU/mL, free tetraiodothyronine was 8.91 mcg/dL, free triiodothyronine was 75.06 ng/dL, and Antithyroid Peroxidase (TPO) was 2.0 IU/ mL. The neck ultrasound revealed the absence of the left thyroid lobe and isthmus. He was diagnosed with congenital TH and hypothyroidism and was treated with a dosage of 25 mcg of levothyroxine. TH can be incidentally discovered and may manifest in later stages of life. Patients with TH are more prone to developing hypothyroidism compared to individuals with a complete thyroid, as they have lower reserves of thyroid hormones.
Role of Nebulised Heparin as an Adjunct in Critically-ill COVID-19 Patients: A Randomised Controlled Trial
Authors: Nagalingareddy Arun , Srividya Peram , Shivakumara KC , Raghu SP
Published: December 2023

Introduction: Coronavirus Disease 2019 (COVID-19) is associated with an increased risk of Venous Thromboembolism (VTE) and coagulopathy. The available studies have shown the anticoagulant and mucolytic effects of nebulised heparin in non COVID-19 patients. Hence it was decided to conducted to study the efficacy of nebulised heparin in patients suffering from COVID-19 pneumonia requiring mechanical ventilation. Aim: To evaluate the safety and efficacy of nebulised heparin administered to patients with COVID-19. Materials and Methods: A double-blinded randomised controlled trial was conducted at Basaveshwara Medical College and Hospital in Chitradurga, Karnataka, India among 100 patients with COVID-19 who required mechanical ventilation from February 2021 to May 2021. They were randomly assigned to two equal groups of 50 patients each. One group received nebulised heparin, and the other group received a placebo. The patients were compared for baseline characteristics, coagulation characteristics, and Oxygen Saturation (SpO2 ). Data were analysed using Statistical Package for Social Sciences (SPSS) version 22.0, expressed as frequency and percentages, and displayed in tables and figures. The association between two variables was determined using the Chi-square test and paired t-test. Results: The two groups did not differ significantly in terms of age, sex, respiratory failure, vasopressin use, and severity score. Respiratory failure was present in 54% of the heparin group and 38% of the placebo group. Vasopressin was used in 64% of the heparin group and 56% of the placebo group. The severity score was 4.44 in the heparin group and 4.42 in the placebo group. Activated Partial Thromboplastin Time (APTT) levels did not differ significantly between the groups. None of these parameters showed significant differences between the heparin and placebo groups. However, both groups showed a significant difference in Thrombin Antithrombin (TAT) complex levels from baseline to follow-up (p<0.05). D-Dimer levels decreased during follow-up, and Spo2 improved significantly in the nebulised heparin group compared to the placebo group. Conclusion: Nebulised heparin used as an adjunct in critically ill COVID-19 patients was shown to decrease TAT and D-Dimer levels. Nebulised heparin also significantly improved oxygenation levels. Importantly, heparin nebulisation was not associated with any adverse events, even when administered with systemic heparin.
Socio-economic determinants of alcohol consumption for South Africa
Authors: Rashied Naiefa
Published: December 2023

Aims: To examine the socio-economic factors associated with alcohol consumption in South Africa.

Design: Cross-sectional study exploring the various socio-economic factors associated with alcohol consumption in South Africa.

Setting: South Africans older than 15 years across the country’s nine provinces.

Participants: Adult respondents of the drinking status and alcohol intensity questions in Wave 4 of the National Income Dynamics Study (NIDS) (n=28 401).

Measures: Alcohol, demographic, emotional, health and neighbourhood variables.

Findings: White and Mixed Heritage (referred to as ‘Coloured’ in South Africa) adults were more likely to consume alcohol, while Indian and White adults were less likely to binge drink relative to African adults. Males with a very good self-perceived health were less likely to binge drink while males who resided in neighbourhoods where frequent alcohol and drug abuse was common, were more likely to binge drink. Females who exercised more than three times a week were also more likely to drink and binge drink. Females with a poor self-perceived health status are less likely to binge drink. Adults who smoked were more likely to drink and binge drink relative to non-smoking adults. Accounting for binge drinkers’ household size, average monthly household spending for binge drinkers was low, suggesting that binge drinkers under-reported household alcohol spending. There was evidence of drinking and binge drinking among pregnant women.

Conclusions: With respect to binge drinking, race, gender, smoking, neighbourhood, self-perceived health, pregnancy and household alcohol spending warrant further investigation and consideration for possible future alcohol interventions in South Africa.
Antifungal Activity of Some Inorganic Salts on the Development of Fusarium spp., Causal Agents of Potato Tuber Dry Rot
Authors: Lionelle Tiaze Fopah Noemie , Elie Keuete Kamdoum , Gaston Tsopmbeng Noumbo
Published: December 2023

Potato dry rot caused by Fusarium spp. is one of the main fungal diseases hampering the production and marketing of potato tubers in Cameroon. This study was carried out in order to improve the health status of potato tubers and their preservation. To achieve this objective, Fusarium spp. were isolated on the Potato Dextrose Agar (PDA) culture medium and identified on the basis of morphological and microscopic characteristics using reference documents. Antifungal activity of six inorganic salts was evaluated in vitro on the development of Fusarium spp. and on potato tubers artificially infected with these fungal species. The results showed that all the inorganic salts had a depressant effect on the development of Fusarium spp. Copper sulfate inhibited at 100%, the radial growth and sporulation of Fusarium spp. at all concentrations. Sodium metabisulfite and sodium carbonate inhibited at 100%, the growth and sporulation of all fungal species from a concentration of 6.4 mg/ml. No lesions were observed on inoculated potato tubers when they were treated with copper sulfate. These results suggest the implementation of a strategy to control dry rot of potato tubers through the use of inorganic salts, in order to reduce the losses caused by Fusarium spp.
Distribution of Papaya Ring Spot Virus Infecting Papaya in Kerala, India
Authors: Joy Josiya , Radhika N. S.  , Johnson Joy Michal , Radhakrishnan N. V.  , Thara Susha S. , Makeshkumar T.  , Beena R.
Published: December 2023

In the midst of the rising interest of papaya cultivation in Kerala, it is inevitable to study the current status of the Papaya ring spot disease in the state. Knowing the severity and distribution of PRSV isolates, causing ring spot disease, helps in the better formulation of effective management strategies against it. Purposive sampling surveys carried out in 2021-22 across five agro ecological units (AEUs) of Kerala, recorded papaya ring spot disease incidence (PRSD) ranging from 50 to 100 per cent in the cultivated areas with vulnerability index of 33.54 to 98.22. Highest disease incidence was recorded from AEU 8- Southern Laterites: Thiruvananthapuram (100.0%) and highest vulnerability index was recorded from Kalliyoor (98.22). Twenty symptomatic samples tested positive for PRSV in double antibody sandwich- ELISA (DAS-ELISA) using PRSV polyclonal antiserum. RT-PCR using coat protein gene specific primers RKJ 52 and 3 yielded amplicons of size approximately ~890bp in all the samples. Virulence of the Kerala isolates was evaluated based on the symptom expression, disease incidence and vulnerability index, upon mechanical transmission of PRSV on two months old papaya plants (variety- Red Lady). PRSV isolate from Kalliyoor (TVM1) inoculated on papaya plants expressed chlorosis, mottling, malformation of leaves and stunting with 96.80 vulnerability index. Maximum vulnerability index and severe symptoms including stunting in the inoculated plants were observed in isolates from southern and central Kerala, which include Thiruvananthapuram, Alappuzha and Thrissur had the most virulent PRSV isolates compared to north Kerala.
Application of Robotics, Artificial Intelligence and Deep Learning in Modern Agriculture Technology: A Review
Authors: Prajapati Harshad A. , Kadam D. M. , Aitwar Shivkanya S. , Jagtap Prathamesh Dilip , Singh Debesh , Nandeha Nirjharnee , Mukherjee Deepanshu
Published: December 2023

In order to determine their potential impact in the field of agriculture, the proposed work aims to review the various artificial intelligence (AI) techniques, with a focus on expert systems, robots designed specifically for agriculture, and sensors technology for data collection and transmission. These techniques include fuzzy logic (FL), artificial neural network (ANN), genetic algorithm (GA), particle swarm optimisation (PSO), artificial potential field (APF), simulated annealing (SA), deep learning. The application of AI techniques and robots in cultivation, monitoring, and harvesting is not highlighted in any literature, making it difficult to compare each one simultaneously based on popularity and usefulness while also understanding how each contributes to the agricultural industry. With knowledge of the extent of AI engaged and the robots used, this paper compares three crucial agricultural phases: cultivation, monitoring, and harvesting. The current study offers a comprehensive analysis of over 200 publications that cover the use of automation in agriculture as of 1960 and 2021. It draws attention to the unmet research needs for developing intelligent, self-governing agricultural systems. The frequency of various AI, robotics and deep learning techniques for particular applications in the agriculture industry round out the article.
Evaluating Second-line ART Efficacy in Pediatric HIV1 Infections: A Study at Albert Royer Children's Hospital
Authors: Baïdy Dieye , Amadou Diop , Ahmet Niang Aïssatou , Abdoulaye Sonko Mouhamadou , Habibou Sarr , Fatoumata Diallo , Gora LO , Roughyatou KA , Halimatou Diop-Ndiaye , Coumba Toure-Kane , Fafa Cisse Moussa , Iyane Sow Ahmad , Bouh Boye Cheikh Saad , Lamine Dia Mouhamadou
Published: December 2023

Introduction: In developing countries, around 15% of children infected with the Human Immunodeficiency Virus (HIV) have access to early diagnosis, and 28% are eligible for antiretroviral treatment (ART). The evaluation studies carried out in Senegal have been limited to children on first-line ART. The main objective of our study was to evaluate the efficacy of second-line ART.

Methodology: Data were collected at 3 different sites. This was a retrospective, longitudinal and analytical study, conducted from March 4 to August 28, 2015. The study population consisted of 65 HIV1-infected children. BD FACSCountTM Flow Cytometer for TCD4 lymphocyte counting. For genotyping, 2 sets of PCRs were required. Data were entered and analysed using Word/Excel 2013 and Epi-info7 software.

Results: We had 43 boys and 22 girls, giving a sex ratio of 1.95. The extreme ages were 5 and 15 years, and the mean age was 11.43 years. The majority belonged to stage 4 and 2 of the WHO classification. The clinical evolution was favourable in 86.15%, unfavourable in 3.07% and unspecified in 10.76%. We found 9 genotypes and recombinant forms; 80% of the strains were sequenced.

Discussion: The general aim of ART is the same as in adults. Clinical stages were not specified in 15.38% of cases. In total, 58.46% had an excellent immunovirological response. We conclude from this that a good IR doesn’t mean a good immunovirological evolution. Initiation of ART should be guided by genotyping.

Conclusion-Recommendations: ART reduced morbidity and mortality. Our study showed a virological failure rate of 21.53% and an IR rate of 86.15%.
Survey of Encroachment of the Benin-Ughelli Transmission Line Right of Way
Authors: Horsfall M. A. S. , Obafemi A. A. , Hart A. I.
Published: December 2023

This study examined the environmental impacts of the 107 km Benin-Delta (Ughelli) 330 kV power transmission line (TL) upgrade project right of way (ROW). Encroachment was determined through ground monitoring and GIS mapping. A total of 83 communities lie within the zone of influence of the transmission line. The communities are 8 in Ethoipe West, 27 in Okpe, 21 in Sapele, 5 in Ughelli North, 1 in Udu, 3 in Uvwie and 18 in Ikpoba Okha. A survey of the communities within the sphere of influence of the TL line revealed that 56 communities had encroached into the transmission line ROW: 5 in Ethoipe West, 9 in Okpe, 15 in Sapele, 5 in Ughelli North, 1 in Udu, 3 in Uvwie and 18 in Ikpoba Okha. The encroachers need to be enlightened on the health implication of building under the TL and the socio-economic consequences that may arise as a result of forceful evacuation from the occupied land.  For the upgrade of the TL, encroachers should be persuaded to vacate the route.
Intra-Regional Trade Potential: An Analysis of the Ecowas Zone
Authors: Ndao Mamadou Saidou
Published: December 2023

The main objective of this paper is to evaluate and analyse the potential of intra-regional trade in the ECOWAS zone. Given the unavailability of data for some countries, only data from 10 countries could be collected over the period 2001-2019. The methodology we used is based essentially on the gravity model, a model whose use in international trade is widely justified with solid theoretical foundations.  The method for calculating countries' trade potential is inspired by the work of Ghazi, T. and Msadfa, Y. (2016). The results obtained show that Nigeria and Côte d'Ivoire top the ranking, respectively 1st and 2nd, of countries whose trade potential is best exploited. In 2001, Ghana ranked 4th and Senegal 3rd, but in the years since, Ghana has improved its position and Senegal has regressed. Countries such as Mali, Burkina Faso and Niger saw their trade potential increase between 2001 and 2019. In contrast, countries such as Guinea and Benin regressed over this period. These results call on the authorities to encourage the relevant economic policies taken for countries that have seen an improvement in their trade potential. On the other hand, countries with slow or low levels of progress need to be supported by effective development programs to improve their position.
The Impact of Social Work Services on the Quality of Care in Mental Health Complex in Jeddah: A Study of Healthcare Professionals’ Perceptions
Authors: Alkhaldi Waseem Mohammed , Abuatallah Ohoud Fouad , AL-Ghamdi Nesreen Abdullah , Allahyani Bandar , Alghamdi Salman Safar , Alqarni Mohammed Ali , Alzahrani Ibrahim Abdullah
Published: December 2023

Aim: This study aims to investigate the influence of social work services on the quality of care at Eradah and Mental Health Complex in Jeddah.

Duration of the Study: This study employs one year of conduction from December 2022 to November 2023.

Methods: A cross-sectional study was conducted using the SERVQUL questionnaire as the main scale to assess the degree of social work influence on the overall quality of the healthcare setting to be distributed among selected healthcare workers.

Results: Among randomly selected 240 healthcare workers, among these, 20.8% were aged between 25 and 30 years, the majority (68.3%) were male, about 45.4% had a bachelor’s degree, also, about 67.5% of them were married, 52.5% were laboratory technicians. The results indicated a moderate healthcare rating with a mean score of 58.29 and a moderate healthcare adherence rating with a mean score of 98.37. The results revealed a significant difference in the quality of healthcare among patients due to education (P-value =0.012) and there was a significant difference with job title (p-value = 0.001). However, no significant differences were observed about age, or marital status.

Conclusion: It can be concluded that social work is a crucial type of work that must be implemented among healthcare workers to enhance cooperation and serve society, it has been found that healthcare adherence was rated as moderate. Nevertheless, variables such as age, gender, education level, and marital status did not exert a substantial impact.
Molecular Phenotyping With Proteomics
Authors: Schweppe Devin K. , Beliveau Brian J. , Hoofnagle Andrew N.
Published: January 2025

This JAMA Insights explores the capability of proteomics to analyze thousands of proteins in patient samples, which could improve clinicians’ understanding of and ability to treat a wide range of diseases.
Removing Ineffective Drugs From the Market
Authors: Tanveer Sarah , Ioannidis John P. A.
Published: January 2025

This Viewpoint examines the removal of ineffective licensed products from the market, specifically discussing the example oral phenylephrine.
Identification Checks and Underage Sales of Tobacco Products in New Jersey, 2019-2022
Authors: Kong Amanda Y. , Hrywna Mary , Ackerman Christopher , Lee Joseph G. L. , Delnevo Cristine D.
Published: January 2025

This cross-sectional study examines compliance with Tobacco 21 laws in New Jersey between 2019 and 2022.
Ophthalmic Complications Associated With the Antidiabetic Drugs Semaglutide and Tirzepatide
Authors: Katz Bradley J. , Lee Michael S. , Lincoff Norah S. , Abel Anne S. , Chowdhary Somya , Ellis Brian D. , Najafi Ahmad , Nguyen John , Seay Meagan D. , Warner Judith E. A.
Published: January 2025

Importance

Nearly 2% of the US population received a prescription for semaglutide in 2023. There has been a recent concern that this drug and other similar medications may be associated with ophthalmic complications.

Objective

To report ophthalmic complications associated with the use of semaglutide or tirzepatide.

Design, Setting, and Participants

This was a retrospective case series. All patients were initially seen in a community setting. Patients experiencing an ophthalmic complication in association with the use of semaglutide or tirzepatide were included in this analysis.

Exposures

Patients described were using either semaglutide or tirzepatide.

Main Outcomes and Measures

Visual acuity and visual field defects.

Results

A total of 9 patients (mean [SD] age, 57.4 [11.6] years; age range, 37-77 years; 5 female [56%]; 4 male [44%]) were included in this study. Seven patients with nonarteritic ischemic anterior optic neuropathy, 1 patient with bilateral papillitis, and 1 patient with paracentral acute middle maculopathy were reported. Atypical features included sequential ischemic optic neuropathy, bilateral disc swelling at presentation, and progressive vision loss.

Conclusions and Relevance

In this case series study, it was not possible to determine if there is a causal link between these drugs and the ophthalmic complications reported. In some cases, it is hypothesized that rapid correction of hyperglycemia induced by these drugs, rather than a toxic effect of the drugs, could be associated with the ophthalmic complications reported.
A Crowded Nasal Cavity
Authors: Barker Cole J. , Branstetter Barton F.
Published: January 2025

A 41-year-old male patient had symptoms of chronic rhinosinusitis lasting several years. Endoscopy revealed edematous mucosa without discrete mass and was followed by a computed tomography scan to assess severity and inform surgical planning. What is your diagnosis?
Characteristics of the Kelch domain containing (KLHDC) subfamily and relationships with diseases
Authors: Pilcher Courtney , Buco Paula Armina V. , Truong Jia Q. , Ramsland Paul A. , Smeets Monique F. , Walkley Carl R. , Holien Jessica K.
Published: January 2025

The Kelch protein superfamily is an evolutionary conserved family containing 63 alternate protein coding members. The superfamily is split into three subfamilies: Kelch like (KLHL), Kelch‐repeat and bric‐a‐bracs (BTB) domain containing (KBTBD) and Kelch domain containing protein (KLHDC). The KLHDC subfamily is one of the smallest within the Kelch superfamily, containing 10 primary members. There is little known about the structures and functions of the subfamily; however, they are thought to be involved in several cellular and molecular processes. Recently, there have been significant structural and biochemical advances for KLHDC2, which has aided our understanding of other KLHDC family members. Furthermore, small molecules directly targeting KLHDC2 have been identified, which act as tools for targeted protein degradation. This review utilises this information, in conjunction with a thorough exploration of the structural aspects and potential biological functions to summarise the relationship between KLHDCs and human disease.
Peripheral blood leukocyte signatures as biomarkers in relapsed ovarian cancer patients receiving combined anti‐CD73/anti‐PD‐L1 immunotherapy in arm A of the NSGO‐OV‐UMB1/ENGOT‐OV30 trial
Authors: Tandaric Luka , Auranen Annika , Kleinmanns Katrin , DePont Christensen René , Vestrheim Thomsen Liv Cecilie , Wogsland Cara Ellen , McCormack Emmet , Mäenpää Johanna , Madsen Kristine , Stampe Petersson Karen , Mirza Mansoor Raza , Bjørge Line
Published: January 2025

Immune checkpoint inhibitors have demonstrated limited efficacy in overcoming immunosuppression in patients with epithelial ovarian cancer (EOC). Although certain patients experience long‐term treatment benefit, reliable biomarkers for responder pre‐selection and the distinction of dominant immunosuppressive mechanisms have yet to be identified. Here, we used a 40‐marker suspension mass cytometry panel to comprehensively phenotype peripheral blood leukocytes sampled over time from patients with relapsed EOC who underwent combination oleclumab (anti‐CD73) and durvalumab (anti‐PD‐L1) immunotherapy in the NSGO‐OV‐UMB1/ENGOT‐OV30 trial. We found that survival duration was impacted by baseline abundances of total peripheral blood mononuclear cells. Longitudinal analyses revealed a significant increase in CD14+CD16− myeloid cells during treatment, with significant expansion of monocytic myeloid‐derived suppressor cells occurring in patients with shorter progression‐free survival, who additionally showed a continuous decrease in central memory T‐cell abundances. All patients demonstrated significant PD‐L1 upregulation over time on most T‐cell subsets. Higher CD73 and IDO1 expression on certain leukocytes at baseline significantly positively correlated with longer progression‐free survival. Overall, our study proposes potential biomarkers for EOC immunotherapy personalization and response monitoring; however, further validation in larger studies is needed.
Synergistic Hybrid‐Ligand Passivation of Perovskite Quantum Dots: Suppressing Reduced‐Dimensionality and Enhancing Optoelectronic Performance
Authors: Han Sanghun , Jeong Woo Hyeon , Seo Gayoung , Choi Seongmin , Lee Dong Gyu , Chae Weon‐Sik , Ahn Hyungju , Lee Tae Kyung , Choi Hyosung , Choi Jongmin , Lee Bo Ram , Kim Younghoon
Published: January 2025

In terms of surface passivation for realizing efficient CsPbI3‐perovskite quantum dot (CsPbI3‐PQD)‐based optoelectronic devices, phenethylammonium iodide (PEAI) is widely used during the ligand exchange. However, the PEA cation, due to its large ionic radius incompatible with the 3D perovskite framework, acts as an organic spacer within polycrystalline perovskites, leading to the formation of reduced dimensional perovskites (RDPs). Despite sharing the identical 3D perovskite framework, the influence of PEAI on the structure of CsPbI3‐PQDs remains unexplored. Here, it is revealed that PEAI can induce the formation of high‐n RDPs (n > 2) within the CsPbI3‐PQD solids, but these high‐n RDPs undergo an undesirable phase transition to low‐n RDPs, leading to the structural and optical degradation of CsPbI3‐PQDs. To address the PEAI‐induced issue, we employ triphenylphosphine oxide (TPPO) as an ancillary ligand during the ligand exchange process. The incorporation of TPPO prevents H2O penetration and regulates the rapid diffusion of PEAI, suppressing the formation of low‐n RDPs. Moreover, TPPO can passivate the uncoordinated Pb2+ sites, reducing the nonradiative recombination. This hybrid‐ligand exchange strategy using both PEAI and TPPO enables realizing efficient and stable CsPbI3‐PQD‐based light‐emitting diode (external quantum efficiency of 21.8%) and solar cell (power conversion efficiency of 15.3%) devices.
Pericytes Promote More Vascularization than Stromal Cells via an Interleukin‐6‐Dependent Mechanism in Microfluidic Chips
Authors: Gonzalez‐Rubio Julian , Kubiza Hannah , Xu Yong , Koenigs‐Werner Hiltrud , Schmitz Mona Sophie , Schedel Michaela , Apel Christian , Jockenhoevel Stefan , Cornelissen Christian G. , Thiebes Anja Lena
Published: January 2025

Pericytes are a key player in vascularization, protecting endothelial cells from external harm and promoting the formation of new vessels when necessary. However, pericytic identity and its relationship with other cell types, such as mesenchymal stromal/stem cells, is highly debated. This study compares the role of pericytes and unselected stromal cells in vascularization using multichannel microfluidic chips. In both angiogenesis and vasculogenesis, pericytes promote more vessel formation than stromal cells. Pericytes can wrap around endothelial vessels acting as mural cells, while stromal cells remain separated. Whole‐transcriptome sequencing confirms an upregulation of pro‐vascularization genes in endothelial cell‐pericyte co‐cultures, while metabolism increases and inflammation decreases in stromal cell co‐cultures. Treatment of stromal‐endothelial cell co‐cultures with either conditioned media or isolated extracellular vesicles from pericytes replicates the increase in vasculogenesis of the direct co‐cultures. Cytokine quantification reveals that interleukin 6 (IL‐6) is significantly increased in pericyte conditions. Blocking it with siltuximab results in a reduction of pericyte vasculogenic potential comparable to stromal cell levels, revealing that pericyte pro‐vascularization is mediated by IL‐6. This study provides new insights into the relationship between pericytes and endothelial cells and the elusive identity of mesenchymal stromal cells. These findings are relevant for both vascular biology and tissue engineering.
Supramolecular Modulation of Tumor Microenvironment Through Host−Guest Recognition and Metal Coordination to Potentiate Cancer Chemoimmunotherapy
Authors: Wu Dan , Zhou Jie , Zhang Zhankui , Cao Yibin , Ping Kunmin , Qi Shaolong , Du Jianshi , Yu Guocan
Published: January 2025

The massive amount of indoleamine 2,3‐dioxygenase 1 (IDO‐1) in tumor cells and tumor‐associated immune cells forms a feedback loop that maintains immunosuppressive tumor microenvironment (ITM) and causes immune escape, resulting in the poor prognosis of platinum chemotherapeutics. However, the effective systemic administration of platinum drugs and IDO‐1 inhibitors is strictly limited by their distinct chemical construction, different pharmacokinetic profiles, and heterogeneous distributions. Herein, a novel supramolecular method with the capability to modulate tumor microenvironment is proposed aiming at potentiating the antitumor efficacy of chemoimmunotherapy. Profiting from the dynamic and reversible merits of noncovalent interactions, IDO‐1 inhibitor (IDOi) and 1,2‐diaminocyclohexane‐platinum(II) (DACHPt) are tailor‐encapsulated into supramolecular nanoparticles (SNPs) with the aid of host−guest recognition and metal coordination, respectively, effectively increasing the drug loading and improving their pharmacokinetics. In addition to the authorized chemotherapeutical effect, DACHPt performs a systemic antitumor immune response, which is further magnified by the IDOi‐reversed ITM to encourage T lymphocyte infiltration, guaranteeing long‐term antitumor immune responses to improve cancer prognosis.
Elevated SPARC Disrupts the Intestinal Barrier Integrity in Crohn's Disease by Interacting with OTUD4 and Activating the MYD88/NF‐κB Pathway
Authors: Wang Jiayu , He Yuxin , Zhu Xingchao , Zhu Jinghan , Deng Zilin , Zhang Huan , Chen Yanjun , Zhang Guangbo , Shi Tongguo , Chen Weichang
Published: January 2025

Disruption of the intestinal epithelial barrier results in increased permeability and is a key factor in the onset and progression of Crohn's disease (CD). The protein SPARC is primarily involved in cell interaction and migration, but its specific role in the intestinal epithelial barrier remains unclear. This study demonstrates that SPARC is significantly overexpressed in both CD patients and murine models of colitis. Furthermore, mice deficient in SPARC exhibits resistance to chemically induced colitis, a phenomenon associated with the modulation of barrier‐associated proteins. Mechanistically, it is elucidated that SPARC competitively binds to OTUD4 in conjunction with MYD88, facilitating the translocation of p65 from the cytoplasm to the nucleus and subsequent activation of the p65‐MLCK/MLC2 pathway, thereby compromising barrier integrity. Additionally, it is identified that the elevated expression of SPARC in CD is regulated via the METTL3‐YTHDF1 axis. These findings indicate that SPARC levels are elevated in patients with CD and in colitis‐induced mice, leading to intestinal barrier damage through direct interaction with OTUD4 and subsequent activation of the MYD88/p65/MLCK/MLC2 signaling pathway. Consequently, targeting SPARC or the OTUD4/MYD88/p65/MLCK/MLC2 axis may offer novel insights into the molecular mechanisms underlying CD and represent a potential therapeutic strategy.
Microneedles at the Forefront of Next Generation Theranostics
Authors: Wang Chan , Yang Yuan , Zhang Jiaqi , Zhang Hanrui , Wang Qian , Ma Shengmei , Zhao Pengfei , Li Zhou , Liu Yuxin
Published: January 2025

Theranostics, combining therapeutic and diagnostic functions, marks a revolutionary advancement in modern medicine, with microneedle technology at its forefront. This review explores the substantial developments and multifaceted applications of microneedles, which have evolved from basic transdermal drug delivery devices to sophisticated diagnostic and therapeutic platforms. Microneedles enhance access to biomarkers via interstitial fluid, enabling real‐time monitoring of physiological conditions, such as glucose and hormone levels, thus facilitating continuous health tracking. The evolution of microneedle design from solid to dissolvable forms broadens their utility from mere drug delivery to complex sensing and therapeutic applications, including insulin delivery for diabetes management, vaccination, and gene therapy. This paper delves into the integration of microneedles with wearable technologies, highlighting their role in closed‐loop systems that combine real‐time monitoring with dynamic, precise therapeutic delivery. By addressing gaps in the literature regarding their integrated diagnostic and treatment capabilities, this review underscores the pivotal role of microneedles in personalizing medicine. It concludes with a visionary perspective on the future trajectory of microneedle technology, emphasizing its potential to revolutionize therapeutic strategies through enhanced efficacy, safety, and patient compliance.
Structural Basis and Mechanism of a Unique Haemophore in the Haem‐Iron Acquisition by Riemerella anatipestifer
Authors: Wang Mengying , Zhang Dandan , Tian Xiu , Tong Jiangyang , Yao Yizhou , Wang Mingshu , Zhu Dekang , Jia Renyong , Chen Shun , Zhao Xinxin , Zhang Shaqiu , Huang Juan , Ou Xumin , Tian Bin , Sun Di , He Yu , Wu Zhen , Ouyang Songying , Liu Mafeng , Cheng Anchun
Published: January 2025

Several bacterial pathogens employ haemophores to scavenge haem from host haemoprotein to obtain an iron source. However, no homologues of well‐characterized haemophores are found in Riemerella anatipestifer, a bacterium belonging to the order Flavobacteriales that encodes haem uptake systems. Herein, a unique haemophore RhuH is characterized in this bacterium. R. anatipestifer used RhuH to grow when duck hemoglobin serves as the sole iron resource. RhuH is secreted as a component of outer membrane vesicles. Recombinant RhuH exhibited a high binding affinity for haem (Kd of 3.44 × 10−11 m) and can extract haem from duck hemoglobin. X‐ray crystallography elucidated the 3D structure of RhuH at 2.85 Å resolution, showing a dimeric conformation with each monomer exhibiting a unique structure. Structure modeling of RhuH‐haem, coupled with mutagenesis, haemin utilization, and binding affinity assays, show that haem is captured in the β‐barrel–like region, displaying the classic iron coordination. The RhuH homologues are predominantly distributed in Weeksellaceae and Flavobacteriaceae. Finally, the homologues of RhuH in Riemerella columbina, Flavobacterium columnare, and Flavobacterium soli are used as a proof of concept, demonstrating that these homologues exhibit conserved structures and functions.
The Multifaceted Roles of BACH1 in Disease: Implications for Biological Functions and Therapeutic Applications
Authors: Wei Xiangxiang , He Yunquan , Yu Yueyang , Tang Sichong , Liu Ruiwen , Guo Jieyu , Jiang Qingjun , Zhi Xiuling , Wang Xinhong , Meng Dan
Published: January 2025

BTB domain and CNC homolog 1 (BACH1) belongs to the family of basic leucine zipper proteins and is expressed in most mammalian tissues. It can regulate its own expression and play a role in transcriptionally activating or inhibiting downstream target genes. It has a crucial role in various biological processes, such as oxidative stress, cell cycle, heme homeostasis, and immune regulation. Recent research highlights BACH1's significant regulatory roles in a series of conditions, including stem cell pluripotency maintenance and differentiation, growth, senescence, and apoptosis. BACH1 is closely associated with cardiovascular diseases and contributes to angiogenesis, atherosclerosis, restenosis, pathological cardiac hypertrophy, myocardial infarction, and ischemia/reperfusion (I/R) injury. BACH1 promotes tumor cell proliferation and metastasis by altering tumor metabolism and the epithelial‐mesenchymal transition phenotype. Moreover, BACH1 appears to show an adverse role in diseases such as neurodegenerative diseases, gastrointestinal disorders, leukemia, pulmonary fibrosis, and skin diseases. Inhibiting BACH1 may be beneficial for treating these diseases. This review summarizes the role of BACH1 and its regulatory mechanism in different cell types and diseases, proposing that precise targeted intervention of BACH1 may provide new strategies for human disease prevention and treatment.
PRDX6 Prevents NNMT Ubiquitination and Degradation as a Nonenzymatic Mechanism to Promote Ovarian Cancer Progression
Authors: Wu Xingyun , Luo Li , Wang Mao , Dong Lixia , Fan Jiawu , Zeng Yan , Li Sijia , Wang Kui
Published: January 2025

Cancer cells cope with oxidative stress for their proliferation and metastasis by equipping antioxidant systems, among which the antioxidant enzymes peroxiredoxins (PRDXs) play crucial roles. However, whether PRDXs exhibit nonenzymatic functions remains unclear. Here, it is shown that the 1‐cysteine PRDX (PRDX6) upregulates nicotinamide N‐methyltransferase (NNMT) to promote the growth and metastasis of ovarian cancer cells, independently of PRDX6's enzymatic activities. Mechanistically, PRDX6 interacts with NNMT to prevent its binding to the E3 ubiquitin ligase tripartite‐motif protein 56 (TRIM56), leading to the inhibition of NNMT ubiquitination at lysine 23 and 210 and suppression of subsequent proteasomal degradation. In addition, PRDX6‐mediated NNMT upregulation activates mitogen‐activated protein kinase (MAPK) signaling, thereby promoting the growth and metastasis of ovarian cancer cells. Notably, PRDX6 overexpression is associated with higher NNMT protein levels in human ovarian cancer tissues and is predictive of poor prognosis of ovarian cancer patients. Overall, the findings illustrate a critical oncogenic mechanism of the antioxidant enzyme PRDX6 in promoting ovarian cancer progression beyond its enzymatic mechanisms.
Length‐Based Stock Assessment of the Mackerel Scad, Decapterus macarellus (Cuvier, 1833) From the Tanzanian Coastal Waters
Authors: Sululu Joseph Salawa , Lugendo Blandina Robert , Tuda Paul , Benno Benaiah Lameck
Published: January 2025

This study aimed to conduct a stock assessment of Decapterus macarellus from Tanzanian coastal waters to determine its current stock status and provide appropriate management recommendations. We used a suite of length‐based methods, including the Electronic Length Frequency Analysis (ELEFAN) programme to estimate growth parameters and catch curves to evaluate exploitation fishing and mortality parameters; Length‐Based Spawning Potential Ratio (LBSPR) to calculate the spawning potential ratio (SPR), length‐based indicators (LBI) to assess sustainable fishing levels and length‐based reference point (LBRP) to determine the target reference point (RP) for stock spawning biomass (SB). The results indicated that this small pelagic species grows fast, with a growth rate (K) of 0.74 year−1 and a growth performance index (Ф′) of 2.88. However, the stock is currently at risk of overfishing due to high fishing pressure (F/M > 1) and an elevated exploitation rate (E = 0.71), which resulted in a very low SPR (SPR = 0.11) and SB below the target RP. Yield‐per‐recruit analysis revealed that the current fishing effort (Fcurr = 2.57) far exceeded the precautionary limit (F0.1) and surpassed the fishing mortality rate that maximizes yield per recruit (Fmax = 1.73). This excessive effort largely impacted mega‐spawners, reducing their proportion in the catch to a critically low percentage (9%). On the basis of these findings, the study recommends reducing the current fishing effort to F0.1 (0.84) by limiting the number of ring nets, implementing seasonal closures during peak spawning periods and operating in deeper waters (40–200 m) to protect juveniles and minimize mega‐spawner capture.
The changing biodiversity of the Arctic flora in the Anthropocene
Authors: Markley Paul T. , Gross Collin P. , Daru Barnabas H.
Published: January 2025

The plants of the circumpolar Arctic occupy a dynamic system that has been shaped by glacial cycles and climate change on evolutionary timescales. Yet rapid climatic change can compromise the floristic diversity of the tundra, and the ecological and evolutionary changes in the Arctic from anthropogenic forces remain understudied. In this review, we synthesize knowledge of Arctic floral biodiversity across the entirety of the region within the context of its climatic history. We present critical gaps and challenges in modeling and documenting the consequences of anthropogenic changes for Arctic flora, informed by data from the Late Quaternary (~20 ka). We found that previous forecasts of Arctic plant responses to climate change indicate widespread reductions in habitable area with increasing shrub growth and abundance as a function of annual temperature increase. Such shifts in the distribution and composition of extant Arctic flora will likely increase with global climate through changes to the carbon cycle, necessitating a unified global effort in conserving these plants. More data and research on the continuity of tundra communities are needed to firmly assess the risk climate change poses to the Arctic.
De Novo Chromosomes 3q and 5q Chromothripsis Leads to a 5q14.3 Microdeletion Syndrome Presentation: Case Report and Review of the Literature
Authors: Corriveau Melina L. , Korb Joshua C. , Michener Sydney L. , Owen Nichole M. , Wilson Erica L. , Kubala Jamie , Turner Alicia , Takacs Danielle S. , Potocki Lorraine , Swann John W. , Xue Mingshan , Dai Hongzheng , Chao Hsiao‐Tuan
Published: January 2025

5q14.3 microdeletion syndrome (MIM#613443) is a neurodevelopmental disorder (NDD) involving copy number loss of multiple genes including Myocyte enhancer factor 2C (MEF2C) gene in the q14.3 region of chromosome 5. Chromosomes 5 and 15 chromothripsis involving 5q14.3 was previously reported in one individual with developmental epileptic encephalopathy (DEE). A complex chromothripsis between chromosomes 3, 5, 7, 9, and 18 that involved 5q14.3 was also reported in a pregnancy complicated by brain and kidney anomalies on fetal ultrasound. Here, we report chromothripsis of chromosomes 3q and 5q involving 5q14.3 in a three‐year‐old female with Lennox–Gastaut syndrome. The chromosomes 3q and 5q chromothripsis was found by trio genome sequencing (GS) and confirmed by fluorescent in situ hybridization (FISH). Notable clinical findings include medically refractory seizures, global developmental delay, increased fluid‐attenuated inversion recovery (FLAIR) signal in the left inferior temporal gyrus, and dysmorphic features. Chromothripsis of chromosomes 3 and 5 was previously recognized in renal cell carcinomas. To the best of our knowledge, this is the first reported case of chromosomes 3q and 5q chromothripsis leading to a developmental epileptic encephalopathy (DEE) due to disruption of 5q14.3. These findings expand chromosomes 3 and 5 chromothripsis as a genomic mechanism underlying 5q14.3 microdeletion syndrome.