bluuebunny/crossref_metadata_2025 huggingface dataset:
γδ T cells in immune‐mediated kidney disease
Authors: Waterhölter Alex , Krebs Christian F. , Panzer Ulf
Published: September 2024

Immune‐mediated kidney diseases, including glomerulonephritis (GN), represent a diverse spectrum of disorders characterized by inflammation within the glomerulus and other renal compartments. Despite recent advances, the immunopathogenesis of these diseases remains incompletely understood. Current therapeutic approaches based on nonspecific immunosuppression often result in suboptimal outcomes and significant side effects, highlighting the need for tailored interventions. The complexity of the immune system extends beyond classical T‐cell immunity, with the emergence of unconventional T cells — γδ T cells, NKT cells, and MAIT cells — that exhibit a semi‐invariant nature and unique functions that bridge innate and adaptive immunity. γδ T cells exhibit unique homing and activation mechanisms and respond to different ligands, implying a multifaceted role in immune regulation. The understanding of γδ T‐cell involvement in kidney disease lags behind conventional T‐cell research. However, advances in immune cell analysis technologies offer promising avenues for elucidating their precise functions. This review synthesizes the current knowledge on γδ T cells in renal diseases, explores potential therapeutic strategies, and presents a roadmap for future research directions.
Reduction in mucosal‐associated invariant T cells (MAIT) in APECED patients is associated with elevated serum IFN‐γ concentration
Authors: Hetemäki Iivo , Sarkkinen Joona , Wong Huai Hui , Heikkilä Nelli , Laakso Saila , Miettinen Simo , Mäyränpää Mikko I. , Mäkitie Outi , Arstila T Petteri , Kekäläinen Eliisa
Published: September 2024

Mucosal‐associated invariant T cells (MAIT) are innate‐like lymphocytes enriched in mucosal organs where they contribute to antimicrobial defense. APECED is an inborn error of immunity characterized by immune dysregulation and chronic mucocutaneous candidiasis. Reduction in the frequency of circulating MAITs has been reported in many inborn errors of immunity, but only in a few of them, the functional competence of MAITs has been assessed. Here, we show in a cohort of 24 patients with APECED, that the proportion of circulating MAITs was reduced compared with healthy age and sex‐matched controls (1.1% vs. 2.6% of CD3+ T cells; p < 0.001) and the MAIT cell immunophenotype was more activated. Functionally the IFN‐γ secretion of patient MAITs after stimulation was comparable to healthy controls. We observed in the patients elevated serum IFN‐γ (46.0 vs. 21.1 pg/mL; p = 0.01) and IL‐18 (42.6 vs. 13.7 pg/mL; p < 0.001) concentrations. Lower MAIT proportion did not associate with the levels of neutralizing anti‐IL‐22 or anti‐IL‐12/23 antibodies but had a clear negative correlation with serum concentrations of IFN‐γ, IL‐18, and protein C‐reactive protein. Our data suggest that reduction of circulating MAITs in patients with APECED correlates with chronic type 1 inflammation but the remaining MAITs are functionally competent.
Systematic literature review of the humanistic and economic burden of focal epilepsy and primary generalized tonic–clonic seizures in adults
Authors: Boccaletti Simona , Lucas Eleanor , Nixon Annabel , Boskovic Nikolina , Di Dato Giorgio
Published: September 2024

This systematic literature review (SLR) assessed the humanistic and economic burden of focal epilepsy and primary generalized tonic–clonic seizures (PGTCS) in adults to evaluate these domains in both populations and identify evidence gaps to inform future research. A search was conducted on December 7, 2022, using MEDLINE and Embase to identify studies published from 2012 onwards reporting humanistic burden (patient‐reported or caregiver‐reported outcomes or utilities, qualitative evaluations), economic burden (productivity loss, caregiver and societal costs of epilepsy), and sleep‐related outcomes. Of the 2830 citations identified, 136 were included. Most studies were in the focal epilepsy population; very few studies reported outcomes in the PGTCS population. The presence of epilepsy‐specific instruments varied based on the domain evaluated. Epilepsy exerted considerable humanistic and economic burden. Indicators of poor disease control (e.g., high seizure frequency, resistance to anti‐seizure medications, polypharmacy) increased epilepsy burden. Seizure frequency and type, disease severity, and polypharmacy also affected work productivity. Adults with epilepsy, particularly focal epilepsy, reported higher indirect costs, more sick days accrued, and early entry into retirement. Caregivers similarly reported high productivity loss and absenteeism related to caregiving duties. The results of this SLR highlight the high humanistic and economic burden of focal epilepsy and PGTCS, although limited data were available for the PGTCS population. The results include patient‐reported outcome data specific to focal epilepsy and PGTCS, expanding the limited humanistic burden evidence identified in previous reviews, and show the effect of poor disease control on individuals' lives and as a driver of indirect costs.

Plain Language Summary

Our systematic literature review identified studies that evaluated the impact of focal epilepsy and primary generalized tonic–clonic seizures on patients and their caregivers. We found that focal epilepsy negatively impacted patients' mental health and sleep and was associated with higher indirect costs and lower work productivity in people with more severe disease. The impact of primary generalized tonic–clonic seizures on patients was rarely reported, and future research is needed.
Total electricity generation dynamics analysis and renewable energy impacts in South Africa
Authors: Mutombo Ntumba Marc‐Alain , Numbi Bubele Papy , Tafticht Tahar
Published: September 2024

This research explores the dynamics of total electricity generation (TEG) in South Africa through an analysis of data from the International Energy Agency database from 1990 to 2020. A comprehensive examination of various energy sources, including coal, oil, biofuels, nuclear, hydro, solar photovoltaic (PV), solar thermal, and wind, is conducted to ascertain their respective contributions to TEG. Employing the R software environment, the study employs a methodical analytical framework encompassing meticulous data preparation, statistical analysis, and model formulation. The data preparation phase involves intricate processes such as structuring, cleansing, and visualization aimed at eliminating stochastic variables and outliers. Missing data are addressed through the application of the Piecewise Cubic Hermite Interpolating Polynomial method. Subsequent statistical analyses are informed by tests for normality and homogeneity of variance, revealing deviations from normality and disparate variances across energy source groups. Consequently, non‐parametric methodologies such as the Kruskal–Wallis test are adopted. Findings underscore the significant role of nuclear energy in TEG despite facing challenges. Model development entails the construction of multiple linear regression models with varying predictor sizes, with Model m06 emerging as the optimal choice, incorporating key predictors such as coal, nuclear, and solar PV. Rigorous diagnostic assessments confirm the robustness of Model m06 and its suitability for TEG prediction. Comparative analysis against actual data validates its superior performance, characterized by minimal errors and high predictive accuracy. The efficacy of Model m06 in capturing TEG dynamics underscores its utility for informing energy planning initiatives. Recommendations derived from the study advocate for prioritizing renewable energy integration, infrastructure investment, research endeavors, monitoring mechanisms, and public awareness campaigns to advance sustainable energy development goals in South Africa.
Debris‐flow fan channel avulsions: An important secondary erosional process along the Ichino‐sawa torrent, Japan
Authors: Tsunetaka Haruka , Hotta Norifumi , Imaizumi Fumitoshi , Hayakawa Yuichi S.
Published: September 2024

Sediment transported from debris‐flow initiation zones is typically stored in a topographic feature called a debris‐flow fan, the formation process of which governs secondary sediment transport further downstream. Although sediment transport from debris‐flow fans can impact sediment regimes and change landforms, the determinants of progressive fan formation are not well constrained. To identify such determinants, this study monitored debris flows and performed topographic surveys of debris‐flow fans in the Ichino‐sawa torrent (Japan) during 2016–2017. In this period, eight debris flows occurred, two of which eroded the existing fan and formed a new channel with a short recurrence interval (~40 days). Consequently, these two cases induced substantial sediment transport further downstream from the fan. The examined rainfall indices did not provide a threshold for diagnosing the occurrence of such sediment transport. Debris flows with a large flow depth and a long duration led to changes in the runout direction and subsequently formed new channels. Before these processes, the existing channel was backfilled and plugged by previous debris flows, forming a steep fan surface around the fan apex. The results suggest that increasing the magnitude and the duration of debris flows potentially triggers sediment transport from fans coupled with channel plugging. The annual sediment transport from the fan exceeded almost all sediment yields of the world rivers and was found comparable with that linked with volcanic eruptions and their aftermath. Thus, the fan‐formation process can induce substantial sediment transport, independent of volcanic perturbations and extreme climatic events, and is dependent on the sediment supply from repeated occurrence of debris flows in the initiation zones.
Tsunami propagation and flooding maps: An application for the Island of Lampedusa, Sicily Channel, Italy
Authors: Borzì Laura , Scala Pietro , Distefano Salvatore , Laksono F. X. Anjar Tri , Manno Giorgio , Innangi Sara , Gamberi Fabiano , Kovács János , Ciraolo Giuseppe , Di Stefano Agata
Published: September 2024

The Mediterranean coastlines are densely populated zones which host key socio‐economic and commercial activities. For this reason, coastal areas are vulnerable sites in case of natural disasters as tsunamis that can strike coasts causing widespread damage to the population and facilities. For these reasons, several studies were performed over the last decade to study the impact of tsunami waves on the coasts. This research assessed the inundation risk due to a tsunami wave which can hit the southeastern coast of Lampedusa Island. The coastal low‐lying geomorphological setting of the southeastern part of the island led to significant socio‐economic growth, but Lampedusa falls within the Mediterranean Sea, a high‐tsunamigenic area, therefore, the need to investigate tsunami propagation and coastal flooding of this sensitive site emerged. For this scope, a calculation chain model was implemented incorporating three steps: the DELFT‐3D software for earthquake effects modelling, MIKE 21 Flow Model FM for nearshore propagation and HEC‐RAS for onshore tsunami inundation modelling. The simulations illustrate the impact of three tsunami scenarios with different magnitudes (Mw 8.5, 7.5, 6.5) generated by hypothetical earthquakes in the Hellenic Arc. In the Mw 8.5 magnitude scenario, significant flooding occurs in the harbour region, with maximum water depths reaching approximately 3.5 m. The maximum water velocity in this scenario reaches about 15 m/s in the eastern portion, adjacent to cliffs impacted by the tsunami wave. In contrast, the Mw 7.5 magnitude scenario demonstrates reduced flooded areas, with the cliffs containing the waves and preventing further flooding. Water depths and velocities in the Mw 7.5 scenario remain minimal. Changes in both propagation and flooding are not significant between scenarios Mw 7.5 and Mw 6.5. This methodology can be employed for more accurate tsunami wave simulations not only in the Mediterranean region but also in various case studies.
Research of recombinant influenza A virus as a vector for Mycoplasma pneumoniae P1a and P30a
Authors: Yu Liang , Yongbo Wang , Shengjun Yang , Jia Tan , Ya Xu , Guoyang Liao , Linna Ma
Published: September 2024

Background

Mycoplasma pneumoniae (MP) is a common respiratory pathogen affecting the longevity of the elderly and the health of children. However, the human vaccine against MP has not been successfully developed till now due to the poor immunogenicity and side effects of MP inactivated or attenuated vaccine. Therefore, it is necessary to develop a MP genetic engineering vaccine with influenza virus strain as vector.

Methods

In this study, the major antigen genes P1a of MP adhesion factor P1(3862‐4554 bases) and P30a of P30(49‐822 bases) were inserted into the nonstructural protein (NS) gene of Influenza A virus strain A/Puerto Rio/8/34(H1N1), PR8 for short, to construct the recombinant vectors NS‐P1a or NS‐P30a. The recombinant pHW2000 plasmids containing NS‐P1a or NS‐P30a were cotransfected with the rest 7 fragments of PR8 into HEK293T cells. After inoculating chicken embryos, the recombinant influenza viruses rFLU‐P1a and rFLU‐P30a were rescued. RT‐PCR and sequencing were used to identify the recombinant viruses. The hemagglutination titers of rFLU‐P1a and rFLU‐P30a were determined after five successive generations in chicken embryos so as to indicate the genetic stability of the recombinant viruses. The morphology of recombinant influenza viruses was observed under electron microscopy.

Results

P1a or P30a was designed to be inserted into the modified NS gene sequence separately and synthesized successfully. RT‐PCR identification of the recombinant viruses rFLU‐P1a and rFLU‐P30a showed that P1a (693 bp), P30a (774 bp), NS‐P1a (1992bp) and NS‐P30a (2073 bp) bands were found, and the sequencing results were correct. After five successive generations, each virus generation has a certain hemagglutination titer (from 1:32 to 1:64), and the band of P1a or P30a can be seen in the corresponding positions. The virus particles under the electron microscope appeared as spheres or long strips connected by several particles, revealing a complete viral membrane structure composed of virus lipid bilayer, hemagglutinin, neuraminidase, and matrix proteins.

Conclusion

The recombinant viruses rFLU‐P1a and rFLU‐P30a which carried the advantaged immune regions of the P1 and P30 genes in MP were successfully constructed and identified. And the genetic stability of rFLU‐P1a or rFLU‐P30a was relatively high. The typical and complete morphology of influenza virus was observed under the electron microscope. Our research provided a foundation for the further development of MP vaccines for human.
What's the story of the elephant? Evaluation of choose‐your‐own‐adventure activities on public perception of human–elephant conflict
Authors: Tan Cedric Kai Wei , Loo Yen Yi , Ahmad Husam Aina Amyrah , Hii Adeline , Wong Ee Phin
Published: September 2024

Choose‐your‐own‐adventure (CYOA) narratives offer immersive experiences that can effectively convey complex conservation concepts, fostering empathy and critical thinking, particularly in addressing issues like human–elephant conflict. Despite their potential, there is limited research on the use of CYOA activities in conservation education. In this study, we created an interactive story centered on elephant conservation, drawing from existing research to distill scientific concepts into engaging narratives and utilizing various modes of delivery (YouTube and live performances) to reach diverse audiences. We conducted postactivity surveys to assess variations in audience perception, learning, and conservation engagement intentions in relation to sociodemographic factors, activity type, and messages encountered. We then modeled the relationships between ordinal responses and explanatory variables using cumulative ordinal mixed models (N = 398). For the YouTube version, we also considered sociodemographic factors (YouTube n = 53, non‐YouTube n = 47). Our findings indicate a preference for live performances over online YouTube activity, with participants gaining knowledge about elephant conservation from both formats. For the YouTube activity, participants strongly agreed that the activity allowed engagement with the character and topic. They also expressed a higher likelihood of participating in several conservation actions, relative to a control group. While CYOA storytelling shows promise for conservation education, challenges remain in simplifying scientific language, assessing its impact on comprehension of complex issues, standardizing outcomes, and effectively communicating knowledge. Further research is recommended to adapt this approach, making it applicable to various audiences and domains beyond conservation.
Mitigating the Prozone‐Like Effect in HLA Antibody Testing: A Case Report of Therapeutic Plasma Exchange for Antibody‐Mediated Rejection Post‐Heart Transplantation
Authors: Grewal Sarah K. , Achram Robert , Nakahara Hirotomo , Roback John D. , Morris Anna B. , Gebel Howard M. , Bray Robert A. , Sullivan H. Cliff
Published: September 2024

Therapeutic plasma exchange (TPE) is a cornerstone treatment for antibody‐mediated rejection (AMR) post‐organ transplantation, aiming to eliminate pathogenic donor‐specific HLA antibodies (DSA). However, limitations in HLA antibody interpretation due to the prozone‐like effect (PLE) can lead to inaccurate assessment of treatment efficacy. We present a case of a heart transplant recipient with suspected AMR, where an unexpected increase in DSA levels post‐TPE prompted investigation into PLE. Solid‐phase Luminex assays were employed to detect HLA antibodies. Serum was run neat as well as after treatment with ethylenediaminetetraacetic acid (EDTA). Nephelometry was used to detect complement levels. Laboratory analysis of pre‐TPE serum revealed higher DSA levels with EDTA treatment, characteristic of PLE. Complement measurements supported complement‐mediated interference in the pre‐TPE sample. This case underscores the importance of being aware that PLE can occur in HLA testing and can impact the interpretation of TPE efficacy for AMR.
Preemptive Approach to Plerixafor Use Is Optimal in Patients With Relapsed/Refractory Germ Cell Tumors Undergoing Peripheral Blood Hematopoietic Stem Cell Collection: Effect on Collection Days, Yields, and Cost
Authors: Sohutskay David O. , Tetrick Anne M. , Goebel W. Scott , Schwering Dave , Reddy Manasa S.
Published: September 2024

Evidence describing the use of plerixafor in the off‐label population of relapsed/refractory germ cell tumors (GCT) is limited. We aim to describe the effect of rescue versus preemptive plerixafor use on apheresis collection days, collection yields, and cost. We retrospectively collected data on 77 consecutive patients (at least 15 years of age) with GCT who underwent peripheral blood stem cell (PBSC) collection for autologous stem cell transplant between January 1, 2020 and May 1, 2022. Depending on insurance approval, plerixafor was given either as “rescue” (after a first apheresis collection of < 5 × 106 CD34+ cells/kg) or as “preemptive” on Day 4 of granulocyte‐colony stimulating factor (G‐CSF) prior to the first apheresis collection, if the Day 4 peripheral blood CD34+ count was < 40 cells/μL. A total of 66% of patients who received preemptive plerixafor completed collection in 1 day, similar to good mobilizers who only needed G‐CSF (71%, p = 0.366). In contrast, all poor mobilizers in the rescue group required at least 2 days of collection and had lower CD34+ cell yields than the preemptive group (7.15 vs. 9.81 × 106/kg, p = 0.0055). A cost analysis revealed that preemptive plerixafor may save approximately $7000 per patient compared with a rescue approach. Preemptive plerixafor in GCT patients undergoing PBSC collection allows relatively poor mobilizers to collect in fewer days and with lower overall cost. Fewer apheresis procedures result in less risk to the patient, increased patient satisfaction, and the ability to schedule more patients within the constraints of staffing.
Efficient acceleration of the convergence of the minimum free energy path via a path‐planning generated initial guess
Authors: Sun Yi
Published: September 2024

We demonstrate that combining a shifted clustering algorithm with a fast‐marching‐based algorithm can generate accurate approximations of the minimum energy path (MEP) given a free energy landscape (FEL). Using this approximation as the initial guess for the MEP, followed by further refinement with the string method (referred to as the fast marching tree (FMT)‐string combined approach), significantly reduces the number of iterations required for MEP convergence. This approach saves substantial time compared to using linear interpolation (LI) for the initial guess. Our method offers a viable solution for obtaining an effective initial guess of the MEP when an approximate or converged FEL is available. This work highlights the potential of applying FMT‐based approaches to extract the MEP in chemical reactions.
Eco‐friendly approaches for synthesis of indolyl 1H‐pyrroles using rice‐husk‐derived carbonaceous sulfonation as the green catalyst
Authors: Nguyen Linh Dieu , Nguyen Khanh Ha , Nguyen Phat Ngoc , Tran Kim Nguyen , Le Diep Dinh , Tran Phuong Hoang , Nguyen Hai Truong
Published: September 2024

BACKGROUND

Amorphous carbon‐bearing sulfonic acid groups (AC–SO3H) are a kind of solid acid that exhibits high acidity and belongs to the new generation of solid acids. The presence of acidic functional groups, including carboxylic acid, phenolic and sulfonic acid groups, allows for several key activities such as strong Brønsted acid properties, high surface area, stability, reusability and recyclability.

RESULTS

In this work, we synthesized indolyl 1H‐pyrroles from indoles, phenylglyoxal monohydrate, 1,3‐diketones and ammonium acetate using rice‐husk‐derived carbonaceous sulfonation (AC–SO3H) as a catalyst. We explored the impact of catalyst quantity, reaction time, solvent, mineral acid and temperature in order to determine the optimal reaction conditions. Additionally, indolyl 1H‐pyrrole derivatives were also synthesized based on the optimal conditions that were completely investigated, and the structure of these synthetic compounds was characterized by 1H‐ and 13C‐nuclear magnetic resonance.

CONCLUSION

The yield of indolyl 1H‐pyrroles was up to 84% in 6 h at 100 °C with the activity of 30 mg AC–SO3H. Besides, based on the optimal conditions, 21 indolyl 1H‐pyrrole derivatives were formed with the high‐yield and green method. The catalyst could be reused multiple times without a significant decrease in catalytic performance. According to the findings from the experiments, a potential mechanism that included a radical process has been suggested. This eco‐friendly approach provided a straightforward and efficient method to produce a variety of indole–pyrrole conjugates in a single step. © 2024 Society of Chemical Industry (SCI).
Chronic exertional compartment syndrome of the forearm diagnosed in a wider spectrum of patients and not seldom with a history of the same diagnosis in the lower legs
Authors: Sjöcrona Louise , Lindorsson Sophia H. , Rennerfelt Kajsa
Published: September 2024

Purpose

To identify patient characteristics associated with forearm chronic exertional compartment syndrome (CECS) and to demonstrate the distribution of intramuscular pressure (IMP) values at 1 min postexercise in a cohort of patients with exercise‐induced forearm pain.

Methods

A consecutive series of 99 patients seeking orthopaedic consultation for chronic exertional forearm pain underwent IMP measurements between 2010 and 2023. The diagnosis of CECS was confirmed (n = 34) or ruled out (n = 65) based on the patient's history, clinical examination and IMP measurements.

Results

There were significantly more male patients in the CECS group than in the group of patients where the diagnosis was ruled out. Furthermore, a significantly higher proportion of the CECS patients had been previously treated for CECS of the lower legs. The most common occupation was office worker (21%), followed by craftsperson (18%). The most common main physical activities were strength training (21%) and cycling (15%). The median (range) 1‐min postexercise IMP values for patients with CECS were 34 (23–68) mmHg for the flexor compartment and 32 (25–67) mmHg for the extensor compartment.

Conclusion

This study demonstrates a more general population of CECS patients compared to previous studies. Notably, more than a fifth of the CECS patients had previously been treated for CECS in the lower legs. Importantly, considering the 95% confidence interval for IMP values in patients without CECS, the most used IMP cutoff value for diagnosing CECS appears to be too high for the forearm compartments.

Level of Evidence

Level II.
Oxidative Challenges Do Not Impact Pheomelanin‐Dependent Coloration in Male Japanese Quails
Authors: Alejandro Vianey , Hernández América , Pérez‐Rodríguez Lorenzo , Montoya Bibiana
Published: September 2024

Colorful traits play an important role in animal communication. Melanin‐based colorations are the most extended color traits in animals and are produced by two types of endogenous melanic pigments: eumelanins and pheomelanins, the last ones being the least studied in the context of communication. The production of pheomelanin requires a semi‐essential amino acid, cysteine, which is also used for the synthesis of an important endogenous antioxidant, glutathione. Hence, it has been proposed that the synthesis of pheomelanin and glutathione may compete for the cysteine available in the organism. In that case, pheomelanic colorations are predicted to be less intense when the individual is facing an oxidative challenge, and therefore, they would provide information on the oxidative status of the bearer. Here, we experimentally evaluated this hypothesis using male Japanese quails (Coturnix japonica) as a model of study, a species with pheomelanin‐based plumage in the breast and cheeks. During feather growth, individuals were exposed to one of three possible conditions: Control (saline), an endogenous oxidative challenge (Escherichia coli lipopolysaccharide injections), or an exogenous oxidative challenge (paraquat injections). Contrary to predictions, we found that: (1) Birds from the three groups exhibited less intense pheomelanic colorations in feathers after the experimental manipulation, and the magnitude of this change did not differ among groups. (2) There was no effect of the experimental treatments on the proportion reduced/oxidized glutathione, an index of oxidative status. (3) Lipid peroxidation was lower after the experimental manipulation, with birds exposed to the paraquat challenge experiencing a stronger decline than other groups. (4) Cysteine and total glutathione levels decreased after the experimental manipulation, with no differences per group in the magnitude of the decline. Taken together the results do not support the hypothesis that oxidative status plays a key role at determining the variation in the intensity of pheomelanic colorations.
The characteristics of general practitioners and geriatricians who take overall responsibility for the care of older patients with multimorbidity
Authors: Kimura Takuma , Matsumura Shinji , Hashimoto Masayoshi , Shinmura Ken
Published: September 2024

Background

Older patients with multimorbidity often seek care from multiple health care providers and visit several medical institutions. Having a primary care provider who takes overall responsibility for their care may be beneficial. We conducted a survey to identify the characteristics of general practitioners and geriatricians who frequently assume such responsibility for older patients with multimorbidity.

Methods

In June 2022, we distributed by mail an anonymous questionnaire to 3300 family medicine specialists, primary care‐certified physicians, and geriatric specialists in Japan. We used a four‐point Likert‐type scale to score items related to conditions and patient backgrounds that pose challenges in treatment, key clinical factors, and important clinical strategies. Modified Poisson regression was used to identify factors associated with frequently assuming overall responsibility for medical care.

Results

Data from 746 physicians were included in the analysis. Factors associated with frequently assuming overall responsibility for medical care of older patients with multimorbidity included providing inpatient ward care (prevalence ratio [PR] 1.237, 95% CI 1.124–1.362), providing home medical care (PR 1.357, 95% CI 1.225–1.504), frequently treating patients over 90 years old (PR 2.043, 95% CI 1.258–3.318), and the overall score for clinical strategies (PR 1.021, 95% CI 1.010–1.033).

Conclusions

General practitioners and geriatricians who frequently assume overall responsibility for the care of older patients with multimorbidity tend to engage significantly in ward and home medical care, often treat patients above 90 years, and employ numerous clinical strategies.
Efficient Synthesis and Comprehensive Characterization of bis‐Pyrazole Derivatives: Including X‐Ray Crystallography and Hirshfeld Surface Analysis
Authors: Boraei Ahmed T. A. , Soliman Saied M. , Haukka Matti , Barakat Assem , Sarhan Ahmed A. M.
Published: September 2024

Straightforward synthetic access to
bis
‐pyrazole derivatives has presented. The titled
bis
‐pyrazole derivative: 3′,5‐diphenyl‐1′,2‐
bis
(5,6,7,8‐tetrahydrobenzo[4,5]thieno[2,3‐d]pyrimidin‐4‐yl)‐1′H,2H‐[3,4′‐
bis
pyrazol]‐5′‐ol 3 was obtained from the reaction of pyran‐2,4‐dione 1 and 4‐hydrazineyl‐5,6,7,8‐tetrahydrobenzo[4,5]thieno[2,3‐d]pyrimidine 2 in ethanol in a one‐step reaction. The other
bis‐pyrazole derivative: 5,5′‐diphenyl‐1′H,2H‐[3,4′‐bispyrazol]‐3′‐ol 5 formed from hydrazinolysis of pyran‐2,4‐dione 1 or (E)‐3‐((allylamino)(phenyl)methylene)‐6‐phenyl‐2H‐pyran‐2,4(3H)‐dione 4 in ethanol. The molecular structure of both compounds elucidated by X‐ray crystallographic identification and spectrophotometric tools. The supramolecular structure of 3 could be described as a hydrogen bonded dimer via O–H…N interactions which are further connected by π…π contacts. Hirshfeld analysis showed the significance of the N…H, O…H, C…H, C…C, N…N, C…O and H…H interactions. These contacts contributed by 14.4%, 3.2%, 16.4%, 3.9%, 1.0%, 0.4% and 42.7%, respectively from the whole interactions occurred in the crystal. The d
norm, shape index and curvedness maps revealed the importance of π–π stacking interactions in the molecular packing where the % C…C is 3.9%. In case of 5, the short N…H, C…H, and H…H contacts contributed by 15.5%–17.0%, 28.3%–36.7% and 37.8%–45%, respectively in the molecular packing.
Steering through the storm: Environmental uncertainty and delivery performance
Authors: Ignatius Joshua , Li Rui , Yin Yunqiang , Jia Kunze
Published: September 2024

We investigate the impact of Typhoon Lekima, a source of environmental uncertainty, on delivery performance, utilizing data from RiRiShun Logistics. We apply a staggered difference‐in‐differences model across low‐complexity and high‐complexity supply chains. The analysis uncovers distinct dynamics throughout the typhoon's forecast, active, and recovery phases. Notably, the active phase experiences less disruption in delivery performance compared to the forecast phase, owing to RiRiShun's wait‐and‐see policy. This approach leads to order accumulation but subsequently enables more effective resource allocation. In the recovery phase, high‐complexity supply chains demonstrate significant improvements, surpassing pre‐disaster performance levels. The study further emphasizes the critical role of two response mechanisms in managing high‐complexity supply chains. Increasing throughput efficiencies at destination centers and implementing transfer centers prove effective in enhancing delivery performance during both the forecast and active phases. However, the simultaneous application of these response mechanisms during the forecast phase unexpectedly reduces performance.
Supplementation with carnosine, a food‐derived bioactive dipeptide, alleviates dexamethasone‐induced oxidative stress and bone impairment via the NRF2 signaling pathway
Authors: Li Xi‐you , Gu Xiao‐yuan , Li Xiao‐min , Yan Jian‐gang , Mao Xin‐liang , Yu Qin , Du Yu‐lan , Kurihara Hiroshi , Yan Chang‐Yu , Li Wei‐xi
Published: September 2024

BACKGROUND

Carnosine, a natural bioactive dipeptide derived from meat muscle, possesses strong antioxidant properties. Dexamethasone, widely employed for treating various inflammatory diseases, raises concerns regarding its detrimental effects on bone health. This study aimed to investigate the protective effects of carnosine against dexamethasone‐induced oxidative stress and bone impairment, along with its underlying mechanisms, utilizing chick embryos and a zebrafish model in vivo, as well as MC3T3‐E1 cells in vitro.

RESULTS

Our findings revealed that carnosine effectively mitigated bone injury in dexamethasone‐exposed chick embryos, accompanied by reduced oxidative stress. Further investigation demonstrated that carnosine alleviated impaired osteoblastic differentiation in MC3T3‐E1 cells and zebrafish by suppressing the excessive production of reactive oxygen species (ROS) and enhancing the activity of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPX). Moreover, mechanistic studies elucidated that carnosine promoted the expression and nuclear translocation of nuclear factor erythroid 2‐related factor 2 (NRF2), thereby facilitating the transcription of its downstream antioxidant response elements, including heme oxyense‐1 (HO‐1), glutamate cysteine ligase modifier (GCLM), and glutamate cysteine ligase catalytic (GCLC) to counteract dexamethasone‐induced oxidative stress.

CONCLUSION

Overall, this study underscores the potential therapeutic efficacy of carnosine in mitigating oxidative stress and bone damage induced by dexamethasone exposure, shedding light on its underlying mechanism of action by activating the NRF2 signaling pathway. © 2024 Society of Chemical Industry.
Prognostic Significance of Human Papillomavirus Genotypes in Oropharyngeal Squamous Cell Carcinoma
Authors: Costantino Andrea , Magnuson Jeffery Scott , Alamoudi Uthman , Haughey Bruce
Published: September 2024

Objectives

The prognostic significance of human papillomavirus (HPV) genotypes in oropharyngeal squamous cell carcinoma (OPSCC) has garnered considerable attention due to the increasing reliance on HPV status for clinical decision‐making. This study aimed to compare the survival outcomes associated with different HPV genotypes in patients with OPSCC relative to HPV‐negative tumors, providing insights into the potential implications for treatment de‐intensification strategies.

Methods

Patients diagnosed with invasive OPSCC were included from the National Cancer Database (NCDB). Patients were stratified based on HPV status and genotype, with HPV‐negative tumors serving as the reference group. Multivariable Cox regression analysis was performed to assess the independent prognostic value of different HPV genotypes.

Results

Th majority of patient were classified as HPV‐positive (N = 17,358, 70.0%), with HPV 16 being the most common genotype (N = 15410/17358, 88.8%) compared with other high‐risk (N = 1217/17,358, 7.0%) and low‐risk (N = 731/17,358, 4.2%) HPV genotypes. A significantly lower risk of death was measured for all HPV‐positive compared with HPV‐negative tumors (HPV 16: adjusted HR 0.51; 95% CI: 0.49–0.54; other high‐risk HPV: adjusted HR 0.56; 95% CI: 0.49–0.63; low‐risk HPV: adjusted HR 0.59; 95% CI: 0.50–0.68; p < 0.001).

Conclusion

This study highlights the significant prognostic value of HPV genotypes in OPSCC, underscoring the superior survival outcomes of HPV‐positive tumors across all genotypes compared with HPV‐negative tumors. Detailed HPV subtype analysis can inform better treatment decisions and support de‐intensification strategies for patients with low‐risk genotypes.

Level of Evidence

3 Laryngoscope, 135:695–704, 2025
Flexible, Electrochemical Skin‐Like Platform for Inflammatory Biomarker Monitoring
Authors: Lourenço Carolina , Moreira Felismina , Igreja Rui , Martins Gabriela
Published: September 2024

Addressing global challenges in wound management has greatly encouraged the emergence of home diagnosis and monitoring devices. This technological shift has accelerated the development of new skin patch sensors for continuous health monitoring. A key requirement is the creation of flexible platforms capable of mimicking human skin features. Here, for the first time, an innovative, highly adaptable electrochemical biosensor with molecularly imprinted polymers (MIPs) is customized for the detection of the inflammatory biomarker interleukin‐6 (IL‐6). The 3‐electrode gold pattern is geometrically standardized onto a 6 µm thick polyimide flexible membrane, an optically transparent, and biocompatible polymeric substrate. Subsequently, a biomimetic sensing layer specifically designed for the detection of IL‐6 target is produced on these transducers. The obtained MIP biosensor shows a good linear response within the concentration range 50 pg mL−1‐50 ng mL−1, with a low limit of detection (8 pg mL−1). X‐ray photoelectron spectroscopy, scanning electron microscopy, and Fourier transform infrared spectroscopy characterizations confirm the modifications of the flexible gold transducer. After optimization, the biosensing device shows remarkable potential in terms of sensitivity, selectivity, and reproducibility. Overall, the integration of a low‐cost electrochemical sensor on biocompatible flexible polymers opens the way for a new generation of monitoring tools with higher accuracy, less invasiveness, and greater patient comfort.
Preparation of Hierarchical Porous Monoliths With High Surface Areas by a Solvent Knitting Strategy
Authors: Zhong Zicheng , Peng Xiaojie , Gao Hui , Hussain Irshad , Wang Xiaoyan , Tan Bien
Published: September 2024

Hierarchical porous hypercrosslinked monoliths (PolyHIPE‐HCP) with ultrahigh specific surface areas are prepared via a solvent knitting strategy. Compared to previous work, the solvent knitting strategy is carried out in a relatively low air‐controlled atmosphere with gradient heating starting from low temperature while using DCM (Dichloromethane) as both a solvent and a cross‐linker, allowing for a slow and controlled cross‐linking process, thereby achieving a BET surface area ranging from 514 to 728 m2 g−1. Scanning electron microscopy (SEM) shows that the knitting process does not affect the presence of macroporous structure in the PolyHIPE. With the introduction of mesopores and micropores, these hierarchical porous monoliths exhibit significant potential for applications in gas adsorption and water treatment. Hence, a universal, simple and low‐cost method to synthesize polymeric monoliths with hierarchically porous structure and higher surface area is proposed, which has fascinating prospects in industrialization.
Individual curved‐needle interstitial template created using three‐dimensional printing for brachytherapy for distal parauterine tumor recurrence
Authors: Zhang Jie , Luo Chunli , Zhang Wenjun , Yan Junfang , Yu Lang , Qiu Jie
Published: September 2024

Background

Achieving a clinically acceptable dose distribution with commercial vaginal applicators for brachytherapy of recurrent parauterine tumors is challenging. However, the application of three‐dimensional (3D) printing technology in brachytherapy has been widely acknowledged and can improve clinical treatment outcomes.

Purpose

This study aimed to introduce an individual curved‐needle interstitial template (ICIT) created using 3D printing technology for high‐dose‐rate (HDR) brachytherapy with interstitial treatment to provide a clinically feasible approach to distal parauterine and vaginal cuff tumors. The entire workflow, including the design, optimization, and application, is presented.

Methods

Ten patients with pelvic cancer recurrence were examined at our center. The vaginal topography was filled with gauze strips soaked in developer solution, and images were obtained using computed tomography (CT) and magnetic resonance imaging (MRI). Curved needle paths were designed, and ICITs were 3D‐printed according to the high‐risk clinical target volume (HRCTV) and vaginal filling model. The dose and volume histogram parameters of the HRCTV (V100, V200, D90, and D98) and organs at risk (OARs) (D2cc) were recorded.

Results

All patients completed interstitial brachytherapy treatment with the 3D‐printed ICIT. One patient experienced vaginal cuff tumor recurrence, and nine patients experienced parametrial tumor recurrence (four on the left and five on the right). We used two to five interstitial needles, and the maximum angle of the curved needle was 40°. No source obstruction events occurred during treatment of these 10 patients. The doses delivered to the targets and OARs of all patients were within the dose limits and based on clinical experience at our center.

Conclusion

The ICIT is a treatment option for patients with distal parauterine tumor recurrence. This method addresses the limitations of vaginal intracavitary and standard interstitial applicators. The ICIT has the advantages of biocompatibility, personalization, and magnetic resonance imaging compatibility.
Optimisation of the hammer throw using parameterised synthetic motion kinematics in a multi‐body simulation
Authors: Schmidtchen Fabian , Daniel Christian , Tiedemann Stefan , Woschke Elmar
Published: September 2024

Hammer throwing is a motorically demanding sport in which the execution of the movement significantly influences the result, that is the throwing distance. There are many approaches for supporting technical training that are based on measurement technology and image capturing. The accelerations and locus curves of the athlete and hammer are recorded and compared. In this article, these methods are supplemented by a multi‐body simulation (MBS) of the hammer throw. The kinematics of the hand movement is described using a parameterized synthetic trajectory. Scalar parameters in the approach allow the trajectory to be modified. With a MBS model of the wire cable and the hammer, the movement of the hammer can be determined by numerical time integration from the hand's trajectory. As a result the final throwing distance after free flight phase can be analyzed. Due to the complex spatial motion of the hammer during the acceleration phase only heuristic methods can be used to optimize the maximum throwing distance. In a final step the optimized movement can be used to improve the athlete's training.
Family strategies for managing childhood cancer: Using traditional and complementary medicine in Southern Egypt
Authors: Farrag Ahmed , Alqudimat Mohammad R. , Hassan Fatma A. A.
Published: September 2024

Background and purpose

The use of traditional and complementary medicine (T&CM) is common in children with cancer globally. We aimed to assess the prevalence, types, reasons, perceived effectiveness, and disclosure rate of T&CM use among children with cancer in Southern Egypt. We also investigated whether T&CM use contributed to delays in initial presentation and treatment.

Materials and methods

A cross‐sectional design was utilized. Data were collected via an interviewer‐administered questionnaire. Eligible children and their caregivers at the South Egypt Cancer Institute were invited to participate.

Results

Eighty‐six children completed the study (response rate = 86%). T&CM use was reported by 52 (60.5%) patients, with six (11.5%) experienced delayed presentation. The reasons for T&CM use were complementary for 37 (71%) and alternative for 15 (29%) of the participants. The types of T&CM used included herbal (63%), nutritional (33%), witchcraft (29%), and religious (19%) therapies. Approximately 48% of users employed multiple T&CM types. Family members recommended T&CM for 60% of the users. Most patients (65%) perceived T&CM as effective, with 71% initiating its use during the early phases of treatment. Almost all participants (98%) reported that healthcare providers did not inquire about T&CM use. T&CM usage was more prevalent among wealthier families (p = .023). There was no significant relationship between T&CM use and patient gender, diagnosis, residence, or paternal educational level.

Conclusions

The significant utilization of T&CM among children with cancer highlights the need for healthcare providers to engage in open and early discussions with families regarding T&CM use.
Early defibrotide therapy and risk factors for post‐transplant veno‐occlusive disease/sinusoidal obstruction syndrome in childhood
Authors: Goto Hironori , Oba Utako , Ueda Tamaki , Yamamoto Shunsuke , Inoue Masataka , Shimo Yu , Yokoyama Satomi , Takase Yusuke , Kato Wakako , Suenobu Souichi , Ihara Kenji , Koga Yuhki , Ohga Shouichi
Published: September 2024

Background

Veno‐occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a life‐threatening complications of hematopoietic cell transplantation (HCT).

Methods

We studied the impact of early defibrotide (DF) therapy on the outcomes of pediatric patients with VOD/SOS after transplantation, focusing on recent immunotherapies. A total of 111 pediatric patients who underwent HCT for malignant disease between February 2017 and March 2023 at Kyushu University Hospital were included.

Results

Among 111 patients of less than 20 years of age who underwent HCT for malignancy at a single institution between 2017 and 2023, VOD/SOS occurred in 25 (23%) patients. VOD/SOS developed more frequently in the post‐DF era (2020–2023, n = 58) than in the pre‐DF era (31% vs. 13%, p = .04). The proportion of patients with relapsed/refractory acute lymphoblastic leukemia (ALL) was higher in the post‐DF era than in the pre‐DF era (44% vs. 8%, p = .04). Early DF therapy that was started at two European Society for Blood and Marrow Transplantation diagnostic criteria reduced the severity of VOD/SOS (p < .01) in comparison to non‐early therapy started at less than two criteria. A multivariate analysis indicated that a history of cytokine release syndrome (odds ratio [OR] = 10.4, p = .01) and juvenile myelomonocytic leukemia (OR = 8.98, p = .04), but not an endothelial activation and stress index (EASIX) score of greater than 0.85, were independent risk factors for VOD/SOS.

Conclusions

Early DF therapy improves the severity and survival outcomes of post‐transplant VOD/SOS in children. However, its incidence is increasing in the era of immunotherapy for progressive diseases.