bluuebunny/crossref_metadata_2025 huggingface dataset:
Navigating Liquidity Risk: An Analysis Of Small And Medium Enterprises Across Lebanon
Authors: Makdissi Riad , Makdissi Elena , Mekdessi Selim
Published: January 2025

Abstract:
This study investigates the liquidity risk management practices of small and medium-sized enterprises (SMEs) in
Lebanon, focusing on the challenges these businesses face in maintaining financial stability amid a volatile
economic landscape. Recognizing the crucial role of SMEs in Lebanon's economic development and job
creation, this research highlights various factors contributing to liquidity risk, including political instability,
limited access to financing, inefficient cash flow management, and the broader economic conditions affecting
business operations.
Using a quantitative research design, data were collected from 150 SME managers across diverse sectors in
Lebanon through a structured questionnaire. The survey aimed to assess managers’ perceptions of liquidity
risk, their experiences with cash flow challenges, and the strategies they employ to mitigate these risks.
Statistical analyses were conducted to identify significant relationships between perceived liquidity risks and
management practices.
The findings reveal that liquidity risk poses a significant threat to the operational viability of SMEs, with a
considerable number of managers reporting difficulties in managing cash flows and meeting short-term
financial obligations. Key challenges identified include delayed payments from customers, high operational
costs, and a lack of financial buffers to absorb economic shocks. The study also found that many SMEs rely
heavily on internal financing, which further exacerbates their liquidity issues.
Importantly, the research emphasizes the necessity of adopting effective liquidity management strategies, such
as robust cash flow forecasting, efficient inventory management, and improved accounts receivable practices.
These strategies are critical for enhancing financial resilience and ensuring that SMEs can navigate periods of
economic uncertainty without jeopardizing their operations.
The study also offers actionable recommendations for policymakers and SME leaders to create a more
supportive environment for liquidity management. This includes advocating for better access to financing
options, promoting financial literacy programs, and encouraging the adoption of modern financial management
tools. By addressing liquidity risk, SMEs can improve their sustainability and contribute more effectively to
Lebanon's economic growth.
Overall, this research provides valuable insights into the liquidity challenges faced by SMEs in Lebanon,
contributing to the broader discourse on financial management in developing economies. The findings serve as a foundation for future research on liquidity risk and its implications for the SME sector in Lebanon and beyond
The Psychological And Financial Determinants Of Success: Leveraging Mindset, Mental Health, And Strategic Financial Planning For Sustainable Growth In Individuals And Communities.
Authors: Animashaun Ayooluwa Tomiwa
Published: January 2025

Success, whether personal or communal, is a multifaceted concept influenced by an intricate interplay of
psychological and financial factors. This paper explores the foundational determinants of success, focusing on
the roles of mindset, mental health, and strategic financial planning. Psychological determinants, such as
growth mindset and emotional resilience, are analyzed for their impact on goal-setting, problem-solving, and
perseverance in the face of adversity. Additionally, the significance of mental health in sustaining motivation,
creativity, and interpersonal relationships is emphasized as a core pillar of individual and collective well-being.
From a financial perspective, the paper examines how sound financial planning and resource management
serve as enablers of long-term success. Through case studies and data-driven insights, it is shown that financial
literacy, budgeting, and investments not only foster economic stability but also reduce stress, thereby
reinforcing psychological wellness.
The integration of psychological and financial dimensions is proposed as a holistic approach to fostering
sustainable growth. The study further discusses actionable strategies that individuals and communities can
adopt, including fostering a supportive environment for mental health, promoting inancial education,
and adopting innovative tools for strategic planning. Ultimately, the paper aims to contribute to a deeper understanding of how psychological well-being and financial acumen, when aligned, can drive lasting success and empower individuals and communities to thrive in an increasingly complex world.
Cognitive offloading benefits eye gaze interaction
Authors: Gauselmann Paula , Frings Christian , Tempel Tobias
Published: June 2023

For some people with strong motor impairments, controlling a computer with the eyes is the only possibility for human‐computer interaction. In addition, gaze control is becoming a new option as an input device for the general population as well because of the increasing availability of eye‐tracking technology. Yet, little is known about additional cognitive demands involved in gaze control and how to handle potentially high demands when using the eyes not only for perception but also for action. The present study shows that cognitive offloading improves performance when using gaze control. Memory for to‐be‐studied items benefitted significantly from saving another set of items just studied before for later restudy. Employing cognitive offloading in a targeted manner may be a useful means to assist in mastering eye‐gaze control.
The forward testing effect after a 1‐day delay across dissimilar video lessons
Authors: Parong Jocelyn , Green C. Shawn
Published: June 2023

Being tested on previously learned material has been shown to enhance the learning of subsequently encountered material (i.e., the forward testing effect). Some cognitive theories predict that the magnitude of the forward testing effect is not dependent on the content in the previously learned and to‐be‐learned material (content‐general theories), while other theories predict that it does depends on the similarity (content‐specific theories). To adjudicate between these broad theories, participants viewed one of four lessons that were similar or dissimilar on two dimensions, academic domain and presentation structure, relative to a second lesson. After the first lesson, participants were either tested or restudied the material. Then they viewed the second lesson and were tested on the material. Results showed an overall forward testing effect across all four lessons, and the magnitude of the effect was not significantly different between the lessons, providing support for content‐general theories of the forward testing effect.
Senate subcommittee hears witnesses call for strengthened workforce
Authors: Knopf Alison
Published: June 2023

The American Society of Addiction Medicine (ASAM) has not missed a chance to promote the Modernizing Opioid Treatment Access Act (M‐OTAA) that would allow office‐based physicians to prescribe methadone for opioid use disorder (OUD). Only opioid treatment programs (OTPs) can prescribe and dispense methadone for OUD, and pharmacies are not allowed to dispense. (OTPs are not opposed to pharmacies dispensing methadone, but they are opposed to office‐based physicians prescribing it.) For more on M‐OTAA, see https://onlinelibrary.wiley.com/doi/10.1002/adaw.33716.
A Photoreceptor‐Based Hydrogel with Red Light‐Responsive Reversible Sol‐Gel Transition as Transient Cellular Matrix
Authors: Hörner Maximilian , Becker Jan , Bohnert Rebecca , Baños Miguel , Jerez‐Longres Carolina , Mühlhäuser Vanessa , Härrer Daniel , Wong Tin Wang , Meier Matthias , Weber Wilfried
Published: June 2023

Hydrogels with adjustable mechanical properties have been engineered as matrices for mammalian cells and allow the dynamic, mechano‐responsive manipulation of cell fate and function. Recent research yields hydrogels, where biological photoreceptors translated optical signals into a reversible and adjustable change in hydrogel mechanics. While their initial application provides important insights into mechanobiology, broader implementation is limited by a small dynamic range of addressable stiffness. Herein, this limitation is overcome by developing a photoreceptor‐based hydrogel with reversibly adjustable stiffness from ≈800 Pa to the sol state. The hydrogel is based on star‐shaped polyethylene glycol, functionalized with the red/far‐red light photoreceptor phytochrome B (PhyB), or phytochrome‐interacting factor 6 (PIF6). Upon illumination with red light, PhyB heterodimerizes with PIF6, thus crosslinking the polymers and resulting in gelation. However, upon illumination with far‐red light, the proteins dissociate and trigger a complete gel‐to‐sol transition. The hydrogel's light‐responsive mechanical properties are comprehensively characterized and it is applied as a reversible extracellular matrix for the spatiotemporally controlled deposition of mammalian cells within a microfluidic chip. It is anticipated that this technology will open new avenues for the site‐ and time‐specific positioning of cells and will contribute to overcome spatial restrictions.
Life is pain: Fibromyalgia as a nexus of multiple liability distributions
Authors: Moscati Arden , Faucon Annika B. , Arnaiz‐Yépez Cayetana , Lönn Sara Larsson , Sundquist Jan , Sundquist Kristina , Belbin Gillian M. , Nadkarni Girish , Cho Judy H. , Loos Ruth J. F. , Davis Lea K. , Kendler Kenneth S.
Published: June 2023

Fibromyalgia is a complex disease of unclear etiology that is complicated by difficulties in diagnosis, treatment, and clinical heterogeneity. To clarify this etiology, healthcare‐based data are leveraged to assess the influences on fibromyalgia in several domains. Prevalence is less than 1% of females in our population register data, and about 1/10th that in males. Fibromyalgia often presents with co‐occurring conditions including back pain, rheumatoid arthritis, and anxiety. More comorbidities are identified with hospital‐associated biobank data, falling into three broad categories of pain‐related, autoimmune, and psychiatric disorders. Selecting representative phenotypes with published genome‐wide association results for polygenic scoring, we confirm genetic predispositions to psychiatric, pain sensitivity, and autoimmune conditions show associations with fibromyalgia, although these may differ by ancestry group. We conduct a genome‐wide association analysis of fibromyalgia in biobank samples, which did not result in any genome‐wide significant loci; further studies with increased sample size are necessary to identify specific genetic effects on fibromyalgia. Overall, fibromyalgia appears to have strong clinical and likely genetic links to several disease categories, and could usefully be understood as a composite manifestation of these etiological sources.
Multi‐polygenic scores in psychiatry: From disorder specific to transdiagnostic perspectives
Authors: Shi Yingjie , Sprooten Emma , Mulders Peter , Vrijsen Janna , Bralten Janita , Demontis Ditte , Børglum Anders D. , Walters G. Bragi , Stefansson Kari , van Eijndhoven Philip , Tendolkar Indira , Franke Barbara , Mota Nina Roth
Published: June 2023

The dense co‐occurrence of psychiatric disorders questions the categorical classification tradition and motivates efforts to establish dimensional constructs with neurobiological foundations that transcend diagnostic boundaries. In this study, we examined the genetic liability for eight major psychiatric disorder phenotypes under both a disorder‐specific and a transdiagnostic framework. The study sample (n = 513) was deeply phenotyped, consisting of 452 patients from tertiary care with mood disorders, anxiety disorders (ANX), attention‐deficit/hyperactivity disorder (ADHD), autism spectrum disorders, and/or substance use disorders (SUD) and 61 unaffected comparison individuals. We computed subject‐specific polygenic risk score (PRS) profiles and assessed their associations with psychiatric diagnoses, comorbidity status, as well as cross‐disorder behavioral dimensions derived from a rich battery of psychopathology assessments. High PRSs for depression were unselectively associated with the diagnosis of SUD, ADHD, ANX, and mood disorders (p < 1e‐4). In the dimensional approach, four distinct functional domains were uncovered, namely the negative valence, social, cognitive, and regulatory systems, closely matching the major functional domains proposed by the Research Domain Criteria (RDoC) framework. Critically, the genetic predisposition for depression was selectively reflected in the functional aspect of negative valence systems (R2 = 0.041, p = 5e‐4) but not others. This study adds evidence to the ongoing discussion about the misalignment between current psychiatric nosology and the underlying psychiatric genetic etiology and underscores the effectiveness of the dimensional approach in both the functional characterization of psychiatric patients and the delineation of the genetic liability for psychiatric disorders.
Nasschemische Bottom‐up Synthese von Graphen‐Nanostreifen mit atompräzisen Nanoporen
Authors: Niu Wenhui , Fu Yubin , Serra Gianluca , Liu Kun , Droste Jörn , Lee Yeonju , Ling Zhitian , Xu Fugui , Cojal González José D. , Lucotti Andrea , Rabe Jürgen P. , Ryan Hansen Michael , Pisula Wojciech , Blom Paul W. M. , Palma Carlos‐Andres , Tommasini Matteo , Mai Yiyong , Ma Ji , Feng Xinliang
Published: June 2023

Die Inkorporation von Nanoporen in Graphen‐Nanostrukturen wurde als effiziente Methode zur Anpassung der Bandlücke und elektronischen Struktur dieser Materialien demonstriert. Allerdings ist die atomgenaue Einbettung uniformer Nanoporen in Graphen‐Nanostreifen (GNS, engl. GNR) auf atomarer Ebene durch Mangel an effizienten Synthesestrategien bislang unterentwickelt. Wir berichten hier vom ersten lösungschemisch dargestellten, vollständig durch Scholl‐Reaktion konjugierten porösen GNS (pGNS), welchen wir durch das atomgenau dargestellte Polyphenylen P1 mit vorinstallierten hexagonalen Makrozyklen zugänglich machen konnten. pGNS enthält periodische Poren im sub‐Nanometerbereich (0.6 nm) mit einem Abstand von 1.7 nm zueinander. Um unsere Synthesestrategie zu untermauern, wurden zwei poröse Modellverbindungen (1 a, 1 b) mit einer zu pGNS identischen Pore erfolgreich dargestellt. Die chemische Struktur und photophysikalischen Eigenschaften von pGNS wurden durch verschiedene spektroskopische Methoden untersucht. Die eingebetteten periodischen Nanoporen vermindern die π‐Konjugation und damit die Interaktion zwischen den Nanostreifen, verglichen mit nicht porösen GNS von ähnlicher Breite. pGNS zeigt demzufolge eine erhöhte Bandlücke und eine verbesserte nasschemische Prozessierbarkeit.
Chiral Carbon Nanodots Can Act as Molecular Catalysts in Chemical and Photochemical Reactions
Authors: Bartolomei Beatrice , Corti Vasco , Prato Maurizio
Published: June 2023

In this work, a microwave synthesis followed by a simple purification process produces a new type of chiral Carbon Nanodots (CNDs). These CNDs are soluble in organic solvents, exhibit amino groups on their surface and display interesting absorption and emission properties along with mirror image profiles in the electronic circular dichroism spectrum. All these features set the stage for CNDs to act as multifunctional catalytic platforms, able to promote diverse chemical transformations. In particular, the outer shell composition of CNDs was instrumental to carry out organocatalytic reactions in an enantioselective fashion. In addition, the redox and light‐absorbing properties of the material are suitable to drive photochemical processes. Finally, the photoredox and organocatalytic activations of CNDs were exploited at the same time to promote a cross‐dehydrogenative coupling. This work demonstrates that CNDs can be used as catalysts to promote multiple reactivities, previously considered exclusive domain of molecular catalysts.
Quantification and persistence of COVID‐19 virus in recently deceased individuals before and after embalming
Authors: Gitto Lorenzo , Middleton Frank A. , Reynolds Erin S. , Thangamani Saravanan , Jaeger Daniel A. , Mihaila Dana M.
Published: June 2023

The COVID‐19 pandemic severely affected the medical education worldwide. The infection risk for medical students and healthcare personnel who work with COVID‐19 positive cadavers or tissues remains unclear. Moreover, COVID‐19 positive cadavers have been rejected by medical schools, adversely impacting the continuum of medical education. Herein, the viral genome abundance in tissues from four COVID‐19 positive donors before and after embalming were compared. Tissue samples were collected from the lungs, liver, spleen, and brain both pre‐ and postembalming. The possible presence of infectious COVID‐19 was determined by inoculating human tissue homogenates onto a monolayer of human A549‐hACE2 cells and observing for cytopathic effects up to 72 h postinoculation. A real‐ time quantitative reverse transcription polymerase chain reaction was performed to quantify COVID‐19 present in culture supernatants. Fully intact viral genome sequence was possible to obtain in samples with higher levels of virus, even several days postmortem. The embalming procedure described above substantially reduces the abundance of viable COVID‐19 genomes in all tissues, sometimes even to undetectable levels. However, in some cases, COVID‐19 RNA can still be detected, and a cytopathic effect can be seen both pre‐ and postembalmed tissues. This study suggests that embalmed COVID‐19 positive cadavers might be used safely with appropriate precautions followed in gross anatomy laboratories and in clinical and scientific research. Deep lung tissue is the best specimen to test for the virus. If the tests on the lung tissues are negative, there is a very low likelihood that other tissues will show positive results.
Hydride‐Enhanced Plating and Stripping of Aluminum from Triflate‐based Organic Electrolytes**
Authors: Slim Zaher , Menke Erik J.
Published: June 2023

In the quest for developing rechargeable aluminum (Al) batteries, reversible Al plating in the absence of active‐halide components is considered an immense challenge. For this reason, the choice of electrolyte has been primarily limited to the highly corrosive chloroaluminate systems based on aluminum trichloride (AlCl3). In this work, we demonstrate reversible room‐temperature Al plating from an active‐halide‐free (AHF) organic electrolyte based on aluminum trifluoromethanesulfonate (Al(OTF)3) and lithium aluminum hydride (LiAlH4) in tetrahydrofuran (THF), as well as its AlCl3 counterpart. From insights obtained by Density Functional Theory (DFT) and Fourier‐Transform Infrared (FTIR) spectroscopy, ionic speciation in the electrolyte is explored, and mechanisms for the underlying electrochemical processes in the trifluoromethanesulfonate (OTF−)‐based electrolytes are proposed. Al plating and stripping were confirmed by optical microscopy, scanning electron microscopy (SEM) and X‐ray diffraction (XRD). Characterizing the Al deposits from either the OTF−‐ or the chloride (Cl−)‐based electrolytes via depth‐profile X‐ray Photoelectron Spectroscopy (XPS) analyses, we find that these deposits consist of metallic Al, aluminum oxide (Al2O3), and either aluminum trifluoride (AlF3) or aluminum chloride (AlxCly) contaminants arising from a reaction with the electrolyte components which occurs during the plating process.
New Insights into Self‐Discharge and Heat Generation in Magnesium Batteries
Authors: Ul Mohsin Ijaz , Riedel Sibylle , Xiu Yanlei , Zhao‐Karger Zhirong , Ziebert Carlos
Published: June 2023

Invited for this month's cover is the group of Dr. Ijaz Ul Mohsin. For the first time, the total heat generation and self‐discharging phenomena of magnesium batteries containing the Chevrel Phase Mo6S8 and organic 14PAQ are compared for different electrolyte solvents using sophisticated calorimetry. Noticeable differences are observed and in tetraglyme solvent stable cycling and fewer self‐discharge phenomena are detected. However, the activation process needs more cycles to achieve the required capacity in the case of the Chevrel Phase. Read the full text of the Research Article at 10.1002/batt.202300137.
Opine dehydrogenases, an underexplored enzyme family for the enzymatic synthesis of chiral amines
Authors: Telek András , Molnár Zsófia , Vértessy Beáta G. , Tasnádi Gábor
Published: June 2023

Opines and opine‐type chemicals are valuable natural products with diverse biochemical roles, and potential synthetic building blocks of bioactive compounds. Their synthesis involves reductive amination of ketoacids with amino acids. This transformation has high synthetic potential in producing enantiopure secondary amines. Nature has evolved opine dehydrogenases for this chemistry. To date, only one enzyme has been used as biocatalyst, however, analysis of the available sequence space suggests more enzymes to be exploited in synthetic organic chemistry. This review summarizes the current knowledge of this underexplored enzyme class, highlights key molecular, structural, and catalytic features with the aim to provide a comprehensive general description of opine dehydrogenases, thereby supporting future enzyme discovery and protein engineering studies.
Phase I study of cisplatin and nanoparticle albumin‐bound‐paclitaxel combined with concurrent radiotherapy in locally advanced esophageal squamous cell carcinoma
Authors: Jiang Hui , Li Qiaoqiao , Chen Baoqing , Xi Mian , Makelike Kanjiebubi , Liu Shiliang , Hu Yonghong , Zhu Yujia
Published: June 2023

Background

This phase I study aimed to assess the safety, dose‐limiting toxicity (DLT), maximum tolerated dose (MTD) and preliminary effect of nanoparticle albumin‐bound (nab)‐paclitaxel in combination with concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma (ESCC).

Methods

Patients with locally advanced ESCC who were ineligible or refused surgery were enrolled. Nab‐paclitaxel (60 mg/m2, 75 mg/m2, and 90 mg/m2) and cisplatin (25 mg/m2) were administered intravenously weekly on days 1, 8, 15, 22, and 29 on the basis of the 3 + 3 dose escalation method. The total dose of radiation was 50–64 Gy. The primary endpoint was the safety of chemotherapy.

Results

The study enrolled 12 patients across three dose levels. No treatment‐related deaths occurred. One patient in the 60 mg/m2 dose level occurred dose‐limiting Grade 3 febrile neutropenia. No DLT was found in the 90 mg/m2 dose level thus the MTD was not reached. The phase II study's recommended dose was 75 mg/m2 based on the available preclinical and clinical data including pharmacokinetics, pharmacodynamics, efficacy, and toxicity. The frequent hematologic toxicities were leukocytopenia (Grade 1–2 of 66.7% and Grade 3–4 of 33.3%), neutropenia (Grade 1–2 of 91.7% and Grade 3–4 of 8.3%). Nonhematologic toxicities were mild and manageable. Overall response rate (ORR) of all patients achieved 100%.

Conclusions

Weekly schedule of cisplatin and nab‐paclitaxel in combination with concurrent radiotherapy showed manageable toxicities and promising antitumor activity in patients with locally advanced ESCC. The recommended dose of nab‐paclitaxel for further studies is 75 mg/m2.
Cuproptosis‐related miRNAs signature and immune infiltration characteristics in colorectal cancer
Authors: Zhu Zhonglin , Guo Tianan , Weng Junyong , Li Shanbao , Zhu Congcong , Zhao Qiuyan , Xu Ye
Published: June 2023

Background

A novel form of cell death termed cuproptosis was proposed recently. miRNAs play important roles in colorectal cancer (CRC). However, their relationships have not been reported.

Methods

miRNAs that negatively regulate 16 cuproptosis regulators were predicted using Targetscan database. The univariate Cox, LASSO, and multivariate Cox regression analyses were performed to select cuproptosis‐related miRNAs. GSEA and ssGSEA analysis was carried out for functional enrichment analysis. The immune cell proportion score (IPS) and the efficiencies of multiple chemotherapy drugs were compared between different risk groups. The CCK8, cell colony, edu, and flow cytometry assays were performed to validate the roles of miRNA. Luciferase reporter assay confirmed the regulatory mechanism of miRNA on cuproptosis.

Results

Six cuproptosis‐related miRNAs (hsa‐miR‐653, hsa‐miR‐216a, hsa‐miR‐3684, hsa‐miR‐4437, hsa‐miR‐641, and hsa‐miR‐552) were screened out for model construction. The risk score could act as an independent prognostic indicator in CRC (p < 0.001, 95% HR = 1.243 (1.129–1.369)). The nomogram could efficiently predict the overall survival rate (AUC = 0.836). Then, the level of immunosuppressive pathways, immunosuppressive cells, stromal‐activated genes, and stromal score was higher in the high‐risk group. The IPS analysis showed a better response to immunotherapy in the low‐risk group. Also, the risk score was closely correlated with efficiencies of multiple chemotherapy drugs. Furthermore, miR‐653 was highly expressed in CRC tissues (p < 0.001), closely correlated with T stage (p < 0.001), metastasis (p < 0.001), and tumor stage (p < 0.001). High expression of miR‐653 predicted a shorter overall survival (p = 0.0282) and disease‐free survival (p = 0.0056). In addition, miR‐653 promoted cell proliferation, inhibited apoptosis, and negatively regulated the expression of DLD through directly binding to the 3’‐UTR of DLD mRNA.

Conclusion

We constructed a cuproptosis‐related miRNA signature for the prediction of CRC patient survival and immunotherapy sensitivity. miR‐653 was highly expressed in CRC tissues, promoted cell proliferation, and inhibited apoptosis by negatively regulating the expression of DLD.
Chromone Containing Hybrid Analogs: Synthesis and Applications in Medicinal Chemistry
Authors: Auti Prashant S. , Jagetiya Sakshi , Paul Atish T.
Published: June 2023

The use of privileged scaffolds has proven beneficial for generating novel bioactive scaffolds in drug discovery program. Chromone is one such privileged scaffold that has been exploited for designing pharmacologically active analogs. The molecular hybridization technique combines the pharmacophoric features of two or more bioactive compounds to avail a better pharmacological activity in the resultant hybrid analogs. The current review summarizes the rationale and techniques involved in developing hybrid analogs of chromone, which show potential in fields of obesity, diabetes, cancer, Alzheimer's disease and microbial infections. Here the molecular hybrids of chromone with various pharmacologically active analogs or fragments (donepezil, tacrine, pyrimidines, azoles, furanchalcones, hydrazones, quinolines, etc.) are discussed with their structure‐activity relationship against above‐mentioned diseases. Detailed methodologies for the synthesis of corresponding hybrid analogs have also been described, with suitable synthetic schemes. The current review will shed light on various strategies utilized for the design of hybrid analogs in the field of drug discovery. The importance of hybrid analogs in various disease conditions is also illustrated.
Design, Synthesis, and Evaluation of Biological Activity of Ferrocene‐Ispinesib Hybrids: Impact of a Ferrocenyl Group on the Antiproliferative and Kinesin Spindle Protein Inhibitory Activity
Authors: Kowalczyk Karolina , Błauż Andrzej , Moscoh Ayine‐Tora Daniel , Hartinger Christian G. , Rychlik Błażej , Plażuk Damian
Published: June 2023

With the aim to combine more than one biologically‐active component in a single molecule, derivatives of ispinesib and its (S) analogue were prepared that featured ferrocenyl moieties or bulky organic substituents. Inspired by the strong kinesin spindle protein (KSP) inhibitory activity of ispinesib, the compounds were investigated for their antiproliferative activity. Among these compounds, several derivatives demonstrated significantly higher antiproliferative activity than ispinesib with nanomolar IC50 values against cell lines. Further evaluation indicated that the antiproliferative activity is not directly correlated with their KSP inhibitory activity while docking suggested that several of the derivatives may bind in a manner similar to ispinesib. In order to investigate the mode of action further, cell cycle analysis and reactive oxygen species formation were investigated. The improved antiproliferative activity of the most active compounds may be assigned to synergic effects of various factors such as KSP inhibitory activity due to the ispinesib core and ability to generate ROS and induce mitotic arrest.
Quasi‐dynamic breathing model of the lung incorporating viscoelasticity of the lung tissue
Authors: Daphalapurkar Nitin , Riglin Jacob , Mohan Arvind , Harris Jennifer , Bernardin John
Published: June 2023

We advanced a novel model to calculate viscoelastic lung compliance and airflow resistance in presence of mucus, accounting for the quasi‐linear viscoelastic stress–strain response of the parenchyma (alveoli) tissue. We adapted a continuum‐based numerical modeling approach for the lung, integrating the fluid mechanics of the airflow within individual generations of the bronchi and alveoli. The model accounts for elasticity of the deformable bronchioles, resistance to airflow due to the presence of mucus within the bronchioles, and subsequent mucus flow. Simulated quasi‐dynamic inhalation and expiration cycles were used to characterize the net compliance and resistance of the lung, considering the rheology of the mucus and viscoelastic properties of the parenchyma tissue. The structure and material properties of the lung were identified to have an important contribution to the lung compliance and airflow resistance. The secondary objective of this work was to assess whether a higher frequency and smaller volume of harmonic air flow rate compared to a normal ventilator breathing cycle enhanced mucus outflow. Results predict, lower mucus viscosity and higher excitation frequency of breathing are favorable for the flow of mucus up the bronchi tree, towards the trachea.
Non‐approximative Kinetics of Triplet‐Triplet Annihilation at Room Temperature: Solvent Effects on Delayed Fluorescence
Authors: Bjelland Victoria M. , Nakashima Harue , Hashimoto Naoaki , Seo Satoshi , Melø Thor B. , Lindgren Mikael
Published: June 2023

The molecular processes taking place during triplet‐triplet annihilation (TTA) in solvents at room temperature are examined in detail. Special attention is paid to modelling of the nonlinear kinetic reactions. Using time‐ and spectrally resolved spectroscopy of DPA and Pt/Pd‐OEP based sensitizer and annihilators, it is shown how the kinetic of parameters, such as the triplet energy transfer (TET) and TTA of the rate‐reactions, can be simulated, measured and fitted, without approximations, using a numerical scheme. Studies of DPA in the solvents DMSO, THF and toluene at room temperature revealed that viscosity/diffusion together with the excited triplet lifetime of the annihilator are the most crucial parameters for high TTA induced delayed fluorescence. From an analysis of the experimentally determined rates an efficiency of 16–40 % was determined for the combined TET and TTA processes using THF, DMSO and toluene as solvents. (DPA=9,10‐diphenylanthracene, OEP=2,3,7,8,12,13,17,18‐octaethyl‐21H,23H‐porphyrin)
Diagnostic value of intraoperative fine‐needle aspiration cytologic diagnosis versus frozen section‐based histopathologic diagnosis in thoracic malignancies: A single institution's experience
Authors: Mohamed Anas , Donthi Deepak , Malik Preeti , Rizvi Areeba , Ali Ahlam , Sutton Ann , Geisinger Kim
Published: June 2023

Background

Primary lung cancer is the leading cause of cancer death in the United States. Most lung cancers are diagnosed in an outpatient setting, but a subset requires intraoperative diagnosis. Two intraoperative diagnostic methods are available, frozen section (FS) and fine needle aspiration (FNA) cytology. This study compares intraoperative FNA cytology and FS based diagnosis in thoracic malignancies within the same clinical practice.

Methods

Pathology reports from thoracic intraoperative FNA cytology or FS (January 2017–December 2019) were reviewed. Resection diagnosis was the gold standard. If unavailable, concurrent biopsy and final FNA cytology diagnosis were the gold standard.

Results

Of 300 FNA specimens (155 patients), 142 (47%) cases were benign, and 158 (53%) were malignant. Adenocarcinoma was the most common malignant diagnosis (40%), followed by squamous cell carcinoma (26%), neuroendocrine tumors (18%), and other (16%). Intraoperative FNA yielded 88% sensitivity, 99% specificity, and 92% accuracy (p < .001).

Of 298 FS specimens (252 patients), 215 (72%) cases were malignant and 83 (28%) were benign. Adenocarcinomas was the most common malignant diagnosis (48%), followed by squamous cell carcinoma (25%), metastatic carcinomas (13%), and other (14%). FS yielded 97% sensitivity, 99% specificity, and 97% accuracy (p < .001).

Conclusion

Our findings confirm FS is the gold standard for intraoperative diagnosis. FNA cytology may be useful as a non‐invasive, inexpensive initial diagnostic tool intraoperatively, given the similar specificity (99% FNA, 99% FS) and accuracy (92% FNA, 97% FS). Negative FNA could be followed by the costlier and invasive FS. We encourage surgeons to utilize intraoperative FNA first.
Frequency of new psychoactive substances in hair and urine samples of individuals subject to drug testing in driving license regranting—A toxicological perspective
Authors: Fels Helena , Musshoff Frank , Graw Matthias , DeVol Don , Wagner Thomas , Holzer Anna
Published: June 2023

In recent years, numerous new psychoactive substances (NPS) have emerged on the illicit drug market. The assumed non‐detectability of these drugs is often a key motivation for individuals subject to drug testing, such as those in driving license regranting programs. In these programs, NPS are not routinely tested for, and thus, subjects who have to prove abstinence from common drugs of abuse might switch to NPS to avoid positive drug tests. The aim of the study was to determine the frequency of these substances in the hair and urine samples of individuals undergoing drug testing in driving license regranting. A total of 1037 samples (577 hair and 460 urine samples) collected from 949 subjects between February 2017 and December 2018 were retrospectively analyzed for designer drugs and synthetic cannabinoids by liquid chromatography–quadrupole‐time‐of‐flight–mass spectrometry (LC‐QTOF‐MS). For a more sensitive analysis of synthetic cannabinoids and their metabolites, additional testing was performed by liquid chromatography–tandem mass spectrometry (LC‐MS/MS). Overall, 42 hair and two urine samples, which were obtained from 40 subjects, tested positive for NPS resulting in a frequency of 4.2%. While synthetic cannabinoids were detected in all cases, designer drugs were only found in three of these cases. With regard to the 577 hair samples analyzed, 7.3% screened positive, whereas only 0.4% of the 460 tested urine samples contained NPS. The results of this study indicate that synthetic cannabinoid use seems to be popular among this population, and therefore, testing for synthetic cannabinoids should be requested more often preferably using hair analysis.
The proof of concept of uninterrupted push‐pull electromagnetic propulsion and energy conversion systems for drones and planet landers
Authors: VR Sanal Kumar , Mariappan Amrith , Thianesh U. K. , Sukumaran Ajith , Kumar Ashish , Lal V. K. Vijil , John Jerin , Sharma Raunak , Singh Sanjay
Published: June 2023

Although numerous models of aerial‐robots/drones and planet landers have been demonstrated to fly autonomously in natural and manmade environments for far‐reaching scientific and technological change to help humankind, no drone flowed yet with a push‐pull dual‐head electromagnetic propulsion (EMP) system ensuring unrestricted flight endurance. The precept of EMP is eminent as it hastens an object using a flowing electrical current, either to charge a field or opposing a magnetic field for locomotive use. Here we present a proof of concept to demonstrate the capability of a newly invented variable speed propulsion and energy conversion system for uninterruptedly generating the reciprocating motion of a magnetic piston by a solar battery‐driven polarity changer timing circuit together with a laser‐based timing circuit for redundancy. The reciprocating crusade of the magnetic piston could be successfully converted into rotary motion to generate continuous power for various multidisciplinary applications on Earth and the other planets effectively in lieu of long‐lasting rechargeable batteries. The proposed concept can also be used for devising various systems and subsystems from underwater to outer space by using light weight supermalloy, which ensures high magnetic fluxes with relatively low current. Lucrative applications include nanomaterial‐enabled locomotive applications. Aerial robots regulated with the EMP system could be used for fostering pharmaceutical florae in the international space station for drug design to negate the recently discovered phenomenon of Sanal flow choking in cardiovascular system at gravity and/or microgravity conditions. This concept is originated from mind and aimed for lucrative product developments of yocto to yotta scale energy systems and beyond by discovering new magnetic materials through the fourth industrial revolution. Herein, a proof of the concept of an unrestricted solar‐battery driven push‐pull electromagnetic propulsion and energy conversion device by use of light weight high power magnetic materials is presented.
Representativeness of Energy Rating acc. to IEC 61853 for Different Locations in Middle and South Europe
Authors: Rivera Mariella , Reise Christian , Kräling Ulli
Published: June 2023

The energy rating standard series IEC 61 853 parts 1–4 provide a procedure to calculate the performance of a photovoltaic (PV) module for six different reference climates. The results, denoted as climate specific energy rating (CSER), aim to predict the module's energy output for a complete year under maximum power point operation. The reference climate profiles shall represent the typical operating conditions of a PV module in a given region. Our study investigates the representativeness of these reference climates profiles for several locations in South and Central Europe. We gathered both ground‐ and satellite‐based data sets from different weather monitoring stations. Using such data for our specific location in Freiburg, Germany, and a specific reference module, we found deviations ranging from 2.0% to 2.9% compared to the CSER using the temperate continental profile. Further, we analyze the annual impact of the loss factors: reflectivity as function of angle of incidence, solar spectrum, ambient temperature, and irradiance on module performance. For an in‐depth PV module benchmarking, we recommend the use of site‐specific meteorological data for an accurate module performance assessment, rather than relying on the more general estimates from the standard procedure, which do not intend to capture site‐specific effects.
Integrating human iPSC‐derived macrophage progenitors into retinal organoids to generate a mature retinal microglial niche
Authors: Usui‐Ouchi Ayumi , Giles Sarah , Harkins‐Perry Sarah , Mills Elizabeth A. , Bonelli Roberto , Wei Guoqin , Ouchi Yasuo , Ebihara Nobuyuki , Nakao Shintaro , Friedlander Martin , Eade Kevin T.
Published: June 2023

In the retina, microglia are resident immune cells that are essential for development and function. Retinal microglia play a central role in mediating pathological degeneration in diseases such as glaucoma, retinitis pigmentosa, age‐related neurodegeneration, ischemic retinopathy, and diabetic retinopathy. Current models of mature human retinal organoids (ROs) derived from iPS cell (hiPSC) do not contain resident microglia integrated into retinal layers. Increasing cellular diversity in ROs by including resident microglia would more accurately represent the native retina and better model diseases in which microglia play a key role. In this study, we develop a new 3D in vitro tissue model of microglia‐containing retinal organoids by co‐culturing ROs and hiPSC‐derived macrophage precursor cells (MPCs). We optimized the parameters for successful integration of MPCs into retinal organoids. We show that while in the ROs, MPCs migrate to the equivalent of the outer plexiform layer where retinal microglia cells reside in healthy retinal tissue. While there, they develop a mature morphology characterized by small cell bodies and long branching processes which is only observed in vivo. During this maturation process these MPCs cycle through an activated phase followed by a stable mature microglial phase as seen by the down regulation of pro‐inflammatory cytokines and upregulation of anti‐inflammatory cytokines. Finally, we characterized mature ROs with integrated MPCs using RNAseq showing an enrichment of cell‐type specific microglia markers. We propose that this co‐culture system may be useful for understanding the pathogenesis of retinal diseases involving retinal microglia and for drug discovery directly in human tissue.
Oligodendrocyte progenitor development from the postnatal rat subventricular zone is regulated by the p75 neurotrophin receptor
Authors: Joshi Subhashini , Frondelli Michelle J. , Zanin Juan P. , Levison Steven W. , Friedman Wilma J.
Published: June 2023

The precise timing of neural progenitor development and the correct balance between proliferation and differentiation are crucial to generating a functional brain. The number, survival, and differentiation of neural progenitors during postnatal neurogenesis and gliogenesis is a highly regulated process. Postnatally, the majority of brain oligodendrocytes are generated from progenitors residing in the subventricular zone (SVZ), the germinal niche surrounding the lateral ventricles. In this study, we demonstrate that the p75 neurotrophin receptor (p75NTR) is highly expressed by OPCs in the postnatal male and female rat SVZ. Whereas the p75NTR is known to initiate apoptotic signaling after brain injury, it is highly expressed by proliferating progenitors in the SVZ, suggesting that it may have a different function during development. Lack of p75NTR reduced progenitor proliferation and caused premature oligodendrocyte differentiation and maturation both in vitro and in vivo, leading to aberrant early myelin formation. Our data reveal a novel role for p75NTR as a rheostat for oligodendrocyte production and maturation during myelin formation in the postnatal rat brain.
The seasonal variation of physical activity and quality of life during the first wave of the COVID‐19 pandemic in Finnish older golfers: A cross‐sectional study
Authors: Kettinen Julia , Venojärvi Mika , Murray Andrew , Tikkanen Heikki
Published: June 2023

Background and Aims

The COVID‐19 pandemic was associated with reduced physical activity and increased sedentary behavior. Golf is a health‐enhancing outdoor exercise and is associated with low risk of viral transmission. The purpose of this study was to describe the seasonal differences in physical activity and quality of life during the first wave of COVID‐19 pandemic in 2020 in Finnish older golfers.

Methods

Older golfers (n = 325) from eight golf clubs retrospectively responded to a questionnaire in summer 2020 on their physical activity and golf activity in winter 2019/20 (pre‐COVID‐19 winter season) and summer season 2020. In addition, they reported their quality of life after the first wave of pandemic in summer 2020. To evaluate the seasonal differences in physical activity, life quality and its association with golf activity, the data were analyzed using the Mann–WhitneyU test, Wilcoxon signed‐rank test, Spearman's correlation test, and linear regression analysis.

Results

Despite COVID‐19 restrictions, golfers' physical activity increased by 24% (p < 0.001) during the COVID‐19 restrictions in the summer of 2020. Moderate physical activity increased by 37% (p < 0.001), walking activity increased by 26% (p < 0.001), and sitting decreased by 21% (p < 0.001) compared with the pre‐COVID‐19 winter season. The full 18‐hole golf round activity was positively associated with moderate physical activity both in the summer and winter season, and with walking in the summer season. Over 90% of golfers reported good quality of life during the 2020 summer restrictions.

Conclusion

In contrast to physical activity levels generally decreasing during the first wave of pandemic, physical activity levels in Finnish golfers increased, and these golfers reported a good quality of life. Golf can provide health enhancing physical activity and older golfers seems to be physically active throughout the year.
Global analysis of the COVID‐19 policy activity levels and evolution patterns: A cross‐sectional study
Authors: Chen Meiqian , Dong Yucheng , Shi Xiaoping , Zhuang Jun
Published: June 2023

Background and Aims

Since the beginning of the coronavirus disease 2019 (COVID‐19), a large number of government policies have been implemented worldwide in response to the global spread of COVID‐19. This paper aims at developing a data‐driven analysis to answer the three research questions: (a) Compared to the pandemic development, are the global government COVID‐19 policies sufficiently active? (b) What are the differences and characteristics in the policy activity levels at the country level? (c) What types of COVID‐19 policy patterns are forming?

Methods

Using the Oxford COVID‐19 Government Response Tracker data set, we present a global analysis of the COVID‐19 policy activity levels and evolution patterns from January 1, 2020 to June 30, 2022, based on the differential expression‐sliding window analysis (DE‐SWAN) algorithm and the clustering ensemble algorithm.

Results

Within the period under study, the results indicate that (a) the global government policy responses to COVID‐19 are very active, and the policy activity levels are significantly higher than those of global pandemic developments; (b) a high activity of policy is positively correlated to pandemic prevention at the country level; and (c) a high human development index (HDI) score is negatively correlated to the country policy activity level. Furthermore, we propose to categorize the global policy evolution patterns into three categories: (i) Mainstream (152 countries); (ii) China; and (iii) Others (34 countries).

Conclusion

This work is one of the few studies that quantitatively explores the evolutionary characteristics of global government policies on COVID‐19, and our results provide some new perspectives on global policy activity levels and evolution patterns.