bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential roles of transformers in brain tumor diagnosis and treatment
Authors: Lan Yu‐Long , Zou Shuang , Qin Bing , Zhu Xiangdong
Published: July 2023

Brain tumor (BT) is one of many malignancies that have substantially enhanced global human morbidity and mortality rates. Early detection and characterization of glioma are essential for effective preventive strategies. Currently, the use of Transformers, a deep learning model for BT diagnosis and treatment, is attracting significant attention. The transformer self‐attention mechanism automatically learns the associations between input data for efficient processing and analysis. Research indicates that Transformers could play an essential role in the BT segmentation of magnetic resonance imaging (MRI) images, the MRI and histopathology‐based grading of brain cancer, BT molecular expression prediction, the classification of primary brain metastasis sites, voxel‐level dose and BT radiotherapy outcome prediction, synergistic prediction, and the pathway deconvolution of drug combinations. In this review, the feasibility, accuracy, and applicability of various algorithms are systematically analyzed and their prospects are discussed. Overall, this review aimed to discuss and provide an overview of the increasing applications of Transformers in real‐time BT detection and therapy, indicating their broad prospects and potential. In the future, Transformers are expected to be increasingly used for the diagnosis and subsequent treatment of BT because of the continuous development and improvement of Transformer‐based deep learning technology. However, more work is required to investigate their properties for anomaly detection, medical image classification, network design development, and application to other medical data.
Granulomatosis with polyangiitis with salivary glands involvement: Presenting a case and describing its clinical, pathophysiological, and therapeutic aspects
Authors: Ahmadzadeh Arman , Farsad Faraneh , Babadi Neda , Mohamadzadeh Dena
Published: July 2023

Key Clinical Message

Granulomatosis with polyangiitis (GPA), a rare form of small vessel vasculitis, may be manifested by multisystem involvement misleading its definitive diagnosis. The involvement of salivary glands is a very rare characteristic of GPA. Herein, we described a case of GPA with submandibular salivary gland involvement followed by reviewing the literature on similar cases. The case was a 31‐year‐old man, a known case of seronegative peripheral arthritis that referred recently with bilateral enlargement of the parotid and submandibular glands. Pulmonary nodules were also evident in the patient's CT scan. Fine‐needle aspiration under ultrasound guidance indicated the presence of degenerated squamoid cells, giant cells, and inflammatory cells with a priority of neutrophils in the submandibular gland, as well as the presence of a cyst containing fluid without the evidence of malignancy in the parotid gland. The positivity for the Anti‐neutrophil Cytoplasmic Antibody (C‐ANCA) marker was also revealed. The patient was treated with methotrexate, prednisolone, and rituximab which led to a gradual reduction in the size of the glands and the improvement of the patient's clinical symptoms within 1 month after the treatment. Enlargement of salivary glands in the context of inflammatory disorders can raise doubts about the existence of GPA, and therefore imaging evaluation and histopathological assessment with an ANCA test will be necessary to confirm or rule out it.
Design and Synthesis of New Type of Macrocyclic Architectures Used for Optoelectronic Materials and Supramolecular Chemistry
Authors: Li Pengfei , Jia Yawei , Chen Pangkuan
Published: July 2023

Supramolecular chemistry has received much attention for decades. Macrocyclic architectures as representative receptors play a vital role in supramolecular chemistry and are applied in many fields such as supramolecular assembly and host‐guest recognition. However, the classical macrocycles generally lack functional groups in the scaffolds, which limit their further applications, especially in optoelectronic materials. Therefore, developing a new design principle is not only essential to better understand macrocyclic chemistry and the supramolecular behaviors, but also further expand their applications in many research fields. In recent years, the doping compounds with main‐group heteroatoms (B, N, S, O, P) into the carbon‐based π‐conjugated macrocycles offered a new strategy to build macrocyclic architectures with unique optoelectronic properties. In particular, the energy gaps and redox behavior can be effectively tuned by incorporating heteroatoms into the macrocyclic scaffolds. In this Minireview, we briefly summarize the design and synthesis of new macrocycles, and further discuss the related applications in optoelectronic materials and supramolecular chemistry.
Unsteady Crossflow during Microfiltration and Its Impact on Fouling Occurrence
Authors: Weinberger Maria E.
Published: July 2023

Der Einsatz und die Wirtschaftlichkeit der Crossflow‐Mikrofiltration werden insbesondere durch das Auftreten von Fouling beeinträchtigt. Eine unstete Überströmung, beispielsweise durch eine pulsierende oder alternierende Betriebsweise, können die Bildung einer Deckschicht verringern und damit einen starken Fluxabfall und den Rückhalt von Gelöststoffen verhindern. Dadurch können insbesondere Prozesse mit geringer Überströmgeschwindigkeit oder hohem Transmembrandruck deutlich verbessert werden. Das Ausmaß der Verbesserung hängt dabei stark von der Foulingneigung des zu filtrierenden Fluids ab.
Emission Properties of Individual AIE‐Luminogens in Solution at Room Temperature†
Authors: Zhao Yuehua , Chen Hongbo , Geng Shaojie , Liu Shunjie , Wang Dapeng
Published: July 2023

Comprehensive Summary

Here, we combined the photon antibunching analysis, fluorescence correlation spectroscopy, and time‐domain fluorescence lifetime imaging microscopy (TD‐FLIM) to study the emission properties of a representative AIE‐luminogen—4,4’‐(benzo[c][1,2,5] thiadiazole‐4,7‐diyl)bis(N,N‐diphenylaniline) (TPA‐BT) at the single emitter level in a tetrahydrofuran (THF)/water solution where water is a non‐solvent for TPA‐BT. Our findings suggest that, at a constant water fraction in the solution, the size of TPA‐BT aggregates increases with the TPA‐BT concentration; TPA‐BT aggregates are not a quantum emitter at room temperature in the solution. Moreover, utilizing TD‐FLIM and a gel trapping technique allowed us to study the fluorescence lifetime of individual TPA‐BT aggregates. Adding a polar solvent like water does not result in an overall decrease in fluorescence lifetime. Rather, it causes the fluorescence lifetime distribution to become wider, and only some molecules experience a decrease in their fluorescence lifetime. These results could represent a step forward in further understanding the photophysics of AIE‐luminogens.
Synthesis and Reactivity of Trifluoromethylthiophosphonium Salts†
Authors: Xu Wen‐Qi , Xu Xiu‐Hua , Qing Feng‐Ling
Published: July 2023

Comprehensive Summary

This article described an unprecedented synthesis of trifluoromethylthiophosphonium salts from allyl trifluoromethyl sulfoxide and phosphines in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) through Mislow‐Evans‐type rearrangement. The resulting trifluoromethylthiophosphonium salts were firstly isolated and fully characterized. These fluoroalkylphosphonium salts, as exemplified by trifluoromethylthio triphenylphosphonium salt (6a), exhibited unique and versatile reaction with nucleophiles and deoxygenative trifluoromethylthiolation reaction of carboxylic acids. Furthermore, the photoredox catalytic tunable radical hydrotrifluoromethylation and hydrotrifluoromethythiolation of unactivated alkenes with 6a was successfully developed.
Relationship between context‐free/in‐context spatial color preferences and color constructs: The extraversion personality trait dimension
Authors: Akbay Saadet , Demirbaş Güler Ufuk
Published: July 2023

Personality traits are considered the primary determinants of emotional and behavioral patterns of individuals within the built environment, influencing the experience of architectural space over their cognitive representation. Specifically, the dimension of extraversion within an individual's personality holds considerable predictive value in determining their attitudes toward the environment. Consequently, this study aims to investigate the influence of personality traits on color preference by comparing preferences for context‐free color samples and in‐context spatial colors among individuals exhibiting varying levels of extraversion. It also aims to ascertain the most accurate color‐construct scale for delineating individuals' preferences for in‐context spatial color. The study employed the International Personality Item Pool (IPIP) representation of lexical factor markers for the Big‐Five structure. For the study, 11 colors, referred to as basic color terms, were selected as stimuli. Data on color preference were obtained through a rank order test for 11 context‐free color samples and 11 virtual images of in‐context spatial colors, as well as ratings of in‐context spatial colors based on 14 color‐construct scales. Findings reveal the relationship between extraversion personality trait and color preferences, revealing distinct patterns between context‐free and in‐context color preferences. They also suggest the possibility of divergent preferences for in‐context spatial colors among individuals with varying levels of extraversion, with certain colors eliciting significantly different ratings on color‐construct scales. The study's findings shed light on the importance of personality traits in predicting the relationship between architectural spaces and colors, depending on individuals' personalities, particularly within design disciplines such as interior architecture.
Comparative Bioavailability of Two Daily Subcutaneous Doses Versus a Single Dose of Intramuscular and Vaginal Progesterone Formulations in Healthy Postmenopausal Females
Authors: Tanguay Mario , Cometti Barbara , Boudreault Sylvie
Published: July 2023

Progesterone is a naturally occurring endocrine hormone. It is used for luteal phase support to improve success rates in assisted reproduction. This was a single‐center, comparative bioavailability, open‐label, randomized, 3‐period, 6‐sequence, crossover study to compare the rate and extent of absorption of subcutaneous (SC) progesterone 25 mg twice daily, versus vaginal (Vag) gel once daily (90 mg progesterone) and 50 mg of intramuscular (IM) progesterone injection once daily in healthy postmenopausal females. Eighteen healthy, postmenopausal, female nonsmokers aged 55–65 years were dosed. Data from 17 subjects who completed at least 2 study periods, including the test and 1 reference, were included in the pharmacokinetic analysis. The SC progesterone product administered twice daily showed a higher exposure than a single dose of the Vag formulation, with least‐squares mean (LSM) ratios (SC/Vag gel) of 219.7% for AUC0–inf and 391.8% for Cmax. The SC progesterone product administered twice daily showed comparable extent of exposure to that of the IM product, but showed higher peak concentration, with LSM ratios (SC/IM) of 92.4% for AUC0–inf and 138.0% for Cmax. Mean (SD) relative bioavailability (Frel) for SC/Vag gel was 449.6 (233.1)%, and for SC/IM was 92.3 (6.3)%. Mild injection site reactions were reported with similar frequency for SC and IM progesterone. With further research, twice‐daily SC progesterone may offer an alternative to existing available treatments for luteal phase support.
Theoretical Considerations for Optimizing the Use of Optogenetics with Complex Behavior
Authors: Glickman Bess , LaLumiere Ryan T.
Published: July 2023

Optogenetic approaches have allowed researchers to address complex questions about behavior that were previously unanswerable. However, as optogenetic procedures involve a large parameter space across multiple dimensions, it is crucial to consider such parameters in conjunction with the behaviors under study. Here, we discuss strategies to optimize optogenetic approaches with complex behavior by identifying critical experimental design considerations, including frequency specificity, temporal precision, activity‐controlled optogenetics, stimulation pattern, and cell‐type specificity. We highlight potential limitations or theoretical considerations to be made when manipulating each of these factors of optogenetic experiments. This overview emphasizes the importance of optimizing optogenetic study design to enhance the conclusions that can be drawn about the neuroscience of behavior. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.
Ribosome Profiling in the Model Diatom Thalassiosira pseudonana
Authors: Pichler Monica , Meindl Andreas , Romberger Markus , Eckes‐Shephard Annemarie , Nyberg‐Brodda Carl‐Fredrik , Buhigas Claudia , Llaneza‐Lago Sergio , Lehmann Gerhard , Hopes Amanda , Meister Gunter , Medenbach Jan , Mock Thomas
Published: July 2023

Diatoms are an important group of eukaryotic microalgae, which play key roles in marine biochemical cycling and possess significant biotechnological potential. Despite the importance of diatoms, their regulatory mechanisms of protein synthesis at the translational level remain largely unexplored. Here, we describe the detailed development of a ribosome profiling protocol to study translation in the model diatom Thalassiosira pseudonana, which can easily be adopted for other diatom species. To isolate and sequence ribosome‐protected mRNA, total RNA was digested, and the ribosome‐protected fragments were obtained by a combination of sucrose‐cushion ultracentrifugation and polyacrylamide gel electrophoresis for size selection. To minimize rRNA contamination, a subtractive hybridization step using biotinylated oligos was employed. Subsequently, fragments were converted into sequencing libraries, enabling the global quantification and analysis of changes in protein synthesis in diatoms. The development of this novel ribosome profiling protocol represents a major expansion of the molecular toolbox available for diatoms and therefore has the potential to advance our understanding of the translational regulation in this important group of phytoplankton. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.

Basic Protocol: Ribosome profiling in Thalassiosira pseudonana

Alternate Protocol: Ribosome profiling protocol for diatoms using sucrose gradient fractionation
Reflection of teachers' feelings of curriculum ownership in their curriculum definitions: The example of Estonia
Authors: Mikser Rain , Viirpalu Piret , Krull Edgar
Published: July 2023

Teachers' feeling of curriculum ownership has been found to be crucial for predicting the success of educational reform initiatives. This study aimed to examine how teachers' feelings of curriculum ownership are reflected in their statements about what they mean by the term ‘curriculum’. We analysed written questionnaire responses from 760 schoolteachers across Estonia. Our qualitative content analysis demonstrated that almost half of the qualified responses defined a curriculum as a mandatory, prescriptive document which does not allow for teachers' high feeling of curriculum ownership. Nearly one‐third of the respondents expressed a moderate feeling of ownership, describing a curriculum as an external guideline but also seeing their own role as active in curriculum implementation. Only about one‐tenth of the respondents expressed a high feeling of ownership in their definitions. In the context of the recent history of curriculum policy in the former socialist European countries, we conclude that the overwhelming rhetoric of the early 1990s related to prioritising teachers' curriculum ownership was in practice quickly and successfully subordinated to globally rising regulatory policies that prioritised external evaluation, benchmarking and standardisation. We will discuss the mechanisms of this phenomenon and the potential avenues for enhancing teachers' curriculum ownership in the context of current education policy realities.
Ketoprofen in horses: Metabolism, pharmacokinetics, and effects on inflammatory biomarkers
Authors: Knych Heather K. , McKemie Daniel S. , Kass Philip H. , Stanley Scott D. , Blea Jeff
Published: July 2023

Ketoprofen is an anti‐inflammatory drug that is commonly administered to racehorses for the alleviation of musculoskeletal pain and inflammation. This study represents a comprehensive examination of the metabolism (in vivo and in vitro), pharmacokinetics and ex vivo pharmacodynamics, of ketoprofen in horses. The in vitro metabolism as well as specific enzymes responsible for metabolism was determined by incubating liver microsomes and recombinant CYP450 and UGT enzymes with ketoprofen. For the in vivo portion, 15 horses were administered a single intravenous dose of 2.2‐mg/kg ketoprofen. Blood and urine samples were collected prior to and up to 120 h post‐drug administration. Additional blood samples were collected at select time points and were stimulated with calcium ionophore or lipopolysaccharide, ex vivo, to induce eicosanoid production. Drug, metabolite, and eicosanoid concentrations were determined using LC–MS/MS. Incubation of ketoprofen with equine liver microsomes generated 3‐hydroxy ketoprofen, an unidentified hydroxylated metabolite, and ketoprofen glucuronide. Recombinant equine CYP2C23 produced the greatest amount of hydroxylated ketoprofen and recombinant equine UGT1A2 generated ketoprofen glucuronide. Dihydro, 3‐hydroxy, and glucuronide metabolites were identified in blood and urine samples. The Vdss was 0.280, 0.385, and 0.319 L/kg for total ketoprofen, S (+) ketoprofen, and R (−) ketoprofen, respectively. The mean half‐life was 6.01 h for total ketoprofen, 2.22 h for S (+) ketoprofen, and 1.72 h for R (−) ketoprofen. Stimulation of ketoprofen‐treated blood with lipopolysaccharide and calcium ionophore resulted in an inhibition of TXB2, PGE2, PGF2alpha, LTB4, and 15(s)‐HETE production for up to 120 h post‐drug administration.
Impact of the Carbon Matrix Composition on the S/C Cathode Porosity and Performance in Prototype Li–S Cells
Authors: Schmidt Florian , Fiedler Magdalena , Arlt Tobias , De Ankita , Hoffmann Florian , Wilde Fabian , Dörfler Susanne , Schumm Benjamin , Abendroth Thomas , Althues Holger , Kaskel Stefan
Published: July 2023

The lithium–sulfur battery is a promising electrochemical storage solution, especially for aviation and aeronautical applications, due to its high‐gravimetric energy density (specific energy) and the abundance of sulfur. In recent years, the number of reported prototype cells and their realized energy have increased. This underlines the progress of technology readiness of the lithium–sulfur system. However, the influence of the cathode porosity as well as the porosity of the carbon material on the performance of prototype cells is still not fully understood. Consequently, in this study, the porosity of solvent‐free processed cathodes is investigated, with varying carbon matrix composition, via mercury intrusion porosimetry and synchrotron tomography. Moreover, the swelling behavior of the S/C dry‐film cathodes is investigated and mitigated. These cathodes are then electrochemically evaluated at pouch cell level with ether‐based electrolytes with varying E/S ratios. The combination of the gained findings in pouch cells enables specific energies of 425 Wh kg−1 and 558 Wh L−1 at cell level.
Study and application of reasonable parameters for hydraulic punching of layer penetration boreholes in Changping Coal Mine
Authors: Min Rui , Chen Xiangjun , Wang Lin , Huang Zhen , Li Haitao
Published: July 2023

Aiming at the application of hydraulic punching technology in soft, low permeability, and high gas coal seams in Changping Coal Mine, there are problems such as large workload, poor permeability enhancement effect, and the formation of “blank zones” in the pressure relief and permeability enhancement areas caused by workers' blind construction. By using a combination of theoretical analysis, numerical simulation, and on‐site practice, the threshold pressure for punching and breaking coal was calculated. The simulation analysis determined the reasonable key parameters for hydraulic punching through layered drilling, providing theoretical support for engineering applications; and the application effect of key parameters was investigated in the 5302 bottom extraction roadway of Changping Coal Mine. The research results show that the threshold value of incident pressure for punching and breaking coal in the No. 3 coal seam of Changping Coal Mine is 4.26 MPa, the reasonable hydraulic punching water pressure is 15 MPa, the punching angle is 60°, the diameter of the punching hole is not more than 0.8 m, and the punching time is 120 min; when the punching water pressure is lower than 4.0 MPa, effective coal flushing cannot be achieved. When the water pressure is between 4.0 and 15.0 MPa, the total amount of coal flushing is positively correlated with the punching water pressure; under the determined reasonable parameter punching conditions, the extraction influence radius is 8.9 m, the effective extraction radius is 5 m, and the average pure gas extraction volume is 0.089 m3/min. Under this parameter, hydraulic punching technology effectively improves the permeability characteristics of coal seams, which is conducive to long‐term gas extraction and has a significant effect on pressure relief and drainage promotion.
Ecotourism impacts on reef fishes in a marine reserve during the COVID‐19 era
Authors: Olán‐González Manuel , Reyes‐Bonilla Héctor , Arreola‐Alarcón I Montserrat , Uribe Regina Valdovinos , Olivier Damien
Published: July 2023

Marine reserves generally permit ecotourism within their boundaries as a source of income for local communities, but the impacts of ecotourism on wildlife are still poorly understood. The lockdown resulting from the COVID‐19 pandemic in 2020 provided a unique opportunity to evaluate wildlife diversity in the absence of human activity. In a marine reserve in Mexico, we monitored fish assemblages before, during, and immediately after the lockdown to examine ecotourism impacts on fish assemblages. Our results show that fish density rose 2.5‐fold during the lockdown, suggesting that ecotourism activities alter fish behavior. We suggest that the presence of divers and noise pollution generated by recreational vessels are important disturbance factors. In the absence of human activity, however, some fish may be more bold (hide less often) or may return to the reserve after having retreated to more tranquil (deepwater) areas. We hope that our findings spur efforts to improve the health of marine reserves through the establishment of effective management strategies to mitigate ecotourism impacts.
Concurrent carboplatin and paclitaxel definitive radiation therapy for locally advanced head and neck cancer
Authors: Han James , Zakeri Kaveh , Raab Gabriel , Hesse Jennifer , Shamseddine Achraf , Chen Linda , Yu Yao , Kang Jung Julie , McBride Sean M. , Riaz Nadeem , Tsai C. Jillian , Gelblum Daphna , Sherman Eric J. , Wong Richard J. , Michel Loren , Lee Nancy Y.
Published: July 2023

Background

We report the outcomes of cisplatin‐ineligible HNSCC patients treated with definitive chemoradiation and concurrent carboplatin and paclitaxel.

Materials and Methods

We included consecutive HNSCC patients treated from 2013 to 2021 that received definitive chemoradiation with carboplatin and paclitaxel. Locoregional recurrences (LRR) and distant metastases (DM) were estimated using cumulative incidence functions. Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan–Meier methods.

Results

Sixty‐five patients were identified with median age of 71 years (range 44–85). Median radiation dose was 70 Gy and the median doses of carboplatin and paclitaxel were AUC 1 and 40 mg/m2, respectively. At a median follow‐up of 29 (range 5–91) months, the 2‐year rates of LRR, DM, PFS, and OS were 8.8%, 9.4%, 72.2%, and 88.7%, respectively. In total, there were 5 LRR, 7 DM, and 12 deaths.

Conclusions

Chemoradiation with carboplatin and paclitaxel is an excellent option for cisplatin‐ineligible HNSCC patients.
Diabetic MAFLD is associated with increased risk of hepatocellular carcinoma and mortality in chronic viral hepatitis patients
Authors: Kim Mi Na , Han Kyungdo , Yoo Juhwan , Hwang Seong Gyu , Zhang Xuehong , Ahn Sang Hoon
Published: July 2023

Metabolic dysfunction‐associated fatty liver disease (MAFLD) can coexist with chronic viral hepatitis. MAFLD is a heterogeneous disease because the diagnostic criteria include various metabolic traits. We aimed to identify patients at high risk of poor long‐term outcomes based on MAFLD subgroups in chronic viral hepatitis patients. We evaluated 63 273 chronic hepatitis B and C patients. Patient with a fatty liver index ≥30 was defined to have hepatic steatosis. MAFLD was defined as the presence of hepatic steatosis with any one of the following three conditions, overweight/obesity, type 2 diabetes or ≥2 metabolic risk factors. The prevalence of MAFLD was 38.4% (n = 24 290). During a median 8.8‐year follow‐up, 1839 HCCs and 2258 deaths were documented in MAFLD patients. Among MAFLD patients, diabetes could identify patients at high risk of HCC and mortality, whereas overweight/obesity and metabolic risk factors did not. Compared with non‐MAFLD patients, risk of HCC and mortality was significantly higher in diabetic MAFLD patients (adjusted hazard ratio [aHR] = 1.34, 95% confidence interval [CI] = 1.26‐1.43 for HCC; aHR = 1.15, 95% CI = 1.08‐1.22 for mortality). Risk of HCC and mortality was significantly higher in diabetic MAFLD patients (aHR = 1.40, 95% CI = 1.26‐1.55 for HCC; aHR = 1.77, 95% CI = 1.63‐1.93 for mortality) compared with non‐diabetic MAFLD patients. Diabetic MAFLD is associated with increased risk of HCC and mortality among chronic viral hepatitis patients. Our findings highlight the need for close surveillance and effective treatment for these high‐risk patients to reduce HCC and mortality in patients with chronic viral hepatitis.
Recent advances in BCRP‐induced breast cancer resistance treatment with marine‐based natural products
Authors: Kanoujia Jovita , Das Anjali , Raina Neha , Kaur Ginpreet , Singh Sandeep K. , Tuli Hardeep S. , Garg Ashish , Gupta Madhu
Published: July 2023

Breast cancer is the prominent cause of cancer‐related death in women globally in terms of incidence and mortality. Despite, recent advances in the management of breast cancer, there are still a lot of cases of resistance to medicines, which is currently one of the biggest problems faced by researchers across the globe. Out of several mechanisms, breast cancer resistance protein (BCRP) arbitrated drug resistance is a major concern. Hormonal, cytotoxic and immunotherapeutic drugs are used in the systemic therapy of breast cancer. It is vital to choose drugs based on the clinical and molecular attributes of the tumor to provide better treatment with greater efficacy and minimal harm. Given the aforementioned necessity, the use of marine flora in treating breast cancer cannot be neglected. The scientists also stressed the value of marine‐derived goods in avoiding breast cancer resistance. Future research into the identification of anticancer drugs will heavily draw upon the marine environment's ample supply of marine‐derived natural products (MNPs), which have a wide range of biological functions. Cell cycle arrest, induction of apoptosis and anti‐angiogenic, anti‐proliferative and anti‐metastasis actions are all part of their processes. The overview of breast cancer, the mechanisms underlying its resistance, recent clinical trials based on marine‐derived products in breast cancer and the use of marine products in the treatment of breast cancer are highlighted in this paper. Moreover, the authors also emphasised the importance of marine‐derived products in preventing breast cancer resistance.
Modest Effects of Osteoclast‐Specific ERα Deletion after Skeletal Maturity
Authors: Doolittle Madison L. , Eckhardt Brittany A. , Vos Stephanie J. , Grain Sarah , Rowsey Jennifer L. , Ruan Ming , Saul Dominik , Farr Joshua N. , Weivoda Megan M. , Khosla Sundeep , Monroe David G.
Published: July 2023

Estrogen regulates bone mass in women and men, but the underlying cellular mechanisms of estrogen action on bone remain unclear. Although both estrogen receptor (ER)α and ERβ are expressed in bone cells, ERα is the dominant receptor for skeletal estrogen action. Previous studies using either global or cell‐specific ERα deletion provided important insights, but each of these approaches had limitations. Specifically, either high circulating sex steroid levels in global ERα knockout mice or the effects of deletion of ERα during growth and development in constitutive cell‐specific knockout mice have made it difficult to clearly define the role of ERα in specific cell types in the adult skeleton. We recently generated and characterized mice with tamoxifen‐inducible ERα deletion in osteocytes driven by the 8‐kb Dmp1 promoter (ERαΔOcy mice), revealing detrimental effects of osteocyte‐specific ERα deletion on trabecular bone volume (−20.1%) and bone formation rate (−18.9%) in female, but not male, mice. Here, we developed and characterized analogous mice with inducible ERα deletion in osteoclasts using the Cathepsin K promoter (ERαΔOcl mice). In a study design identical to that with the previously described ERαΔOcy mice, adult female, but not male, ERαΔOcl mice showed a borderline (−10.2%, p = 0.084) reduction in trabecular bone volume, no change in osteoclast numbers, but a significant increase in serum CTx levels, consistent with increased osteoclast activity. These findings in ERαΔOcl mice differ from previous studies of constitutive osteoclast‐specific ERα deletion, which led to clear deficits in trabecular bone and increased osteoclast numbers. Collectively, these data indicate that in adult mice, estrogen action in the osteocyte is likely more important than via the osteoclast and that ERα deletion in osteoclasts from conception onward has more dramatic skeletal effects than inducible osteoclastic ERα deletion in adult mice. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Who prefers what? Correlates of preferences for next‐generation HIV prevention products among a national U.S. sample of young men who have sex with men
Authors: Biello Katie B. , Valente Pablo K. , da Silva Daniel Teixeira , Lin Willey , Drab Ryan , Hightow‐Weidman Lisa , Mayer Kenneth H. , Bauermeister José A. ,   the iTech Team
Published: July 2023

Introduction

Pre‐exposure prophylaxis (PrEP) has been available for young people for over a decade, yet only ∼15% of young people in the United States with indications for PrEP have a prescription for it. Next‐generation PrEP modalities may address some of the challenges of daily oral PrEP. However, preferences for these products are unknown.

Methods

From October 2020 to June 2021, we conducted an online survey of 737 cisgender, young men who have sex with men (age 15–24 years) without HIV across the United States who reported same‐sex attraction or consensual sex with another man in the past 6 months. Participants completed a conjoint experiment comparing daily oral pills, event‐driven oral pills, event‐driven rectal douches, intramuscular injections, intravenous broadly neutralizing antibody (bnAb) infusions and subcutaneous implants. Participants ranked the products from most to least preferred. Exploded logit models examined the association between ranked preferences of PrEP modalities and socio‐demographic and behavioural characteristics.

Results

Participants’ mean age was 21 years (SD = 2.3), and 56% identified as White. Nineteen percent were currently taking daily oral PrEP, and another 9% had previously taken it. Participants prioritized efficacy, absence of side effects and costs in the conjoint analyses. Daily oral PrEP had the highest preference ranking, followed by event‐driven oral (OR = 0.89, p = 0.058), injectable (OR = 0.83, p = 0.005), implant (OR = 0.48, p < 0.0001), bnAb infusions (OR = 0.38, p < 0.0001) and rectal douches (OR = 0.24, p < 0.0001). There were differences in PrEP preferences across age, insurance status, sexual behaviour, PrEP use history, HIV and sexually transmitted infection (STI) testing history, and STI diagnoses (omnibus tests: p < 0.05). Participants also provided reasons for selecting their top product choice: ease of use for those who chose daily oral (99%) and daily event‐driven (98.5%); feel more protected against HIV for those who chose injectable (95.4%) and implants (100%); not worrying about forgetting to take it for those who chose bnAbs (93.8%); and being able to stop taking it when they want for those who chose rectal douche (90.9%).

Conclusions

Next‐generation modalities were less likely to be preferred over daily oral PrEP, with differences in the magnitude by socio‐demographic and behavioural characteristics. Given the low uptake of daily oral PrEP, end‐users’ preferences for and concerns about PrEP products must be understood to ensure high acceptability and penetration.
U.S. patient preferences for long‐acting HIV treatment: a discrete choice experiment
Authors: Graham Susan M. , Barthold Douglas , Hauber Brett , Brah Aaron T. , Saldarriaga Enrique , Collier Ann C. , Ho Rodney J. Y. ,   the Emory PREFER Team, Marconi Vincent C. , Simoni Jane M.
Published: July 2023

Introduction

Recent advances in long‐acting antiretroviral therapy (LA‐ART) could provide new options for HIV treatment and reduce adherence barriers, if regimens are acceptable to patients. We elicited preferences for key attributes of potential LA‐ART regimens among people with HIV (PWH) in the United States, focusing on four treatment modes (oral tablets, subcutaneous injections, intramuscular injections, and implants), product characteristics and location of administration.

Methods

A discrete choice experiment was conducted among PWH aged ≥18 years recruited from HIV clinics in Washington State and Atlanta, Georgia from March 2021 to June 2022. Participants responded to 17 choice scenarios, each with three options: two systematically generated hypothetical LA‐ART regimens and a constant opt‐out (their current daily oral treatment). LA‐ART regimen descriptions included treatment mode, pain, dosing frequency, location, pre‐treatment time with undetectable viral load, pre‐treatment negative reaction testing and “late‐dose leeway” (i.e. flexibility or forgiveness in timing the next dose). We used conditional logistic regression, with an interaction between treatment mode and pain, to estimate preference weights for all attribute levels.

Results

Seven hundred participants (350 at each site) enrolled, with median age 51 years (range 18–73); 70% identified as cisgender male, 24% as cisgender female and 6% as non‐binary or transgender. LA oral tablets were the only mode preferred over current daily oral treatment, with annual implants and injections the next most preferred LA‐ART option. Longer time between doses was preferred, and administration at home was preferred to clinics, which were preferred to pharmacies. Attributes with less impact on preferences included oral lead‐in treatment to achieve viral suppression or test for negative reactions and late‐dose leeway around the prescribed dosing interval. Participants in Atlanta were more likely to prefer their current daily oral ART than participants from Seattle.

Conclusions

PWH in the United States may soon have several options for LA‐ART. Our results suggest that LA oral tablets will be preferred by many patients over their current daily oral treatment, while implants and injections with longer duration may be acceptable to some. Future research should investigate sources of preference heterogeneity and actual uptake of and adherence to LA‐ART products, when available.
Preparing for long‐acting PrEP delivery: building on lessons from oral PrEP
Authors: Celum Connie , Grinsztejn Beatriz , Ngure Kenneth
Published: July 2023

Introduction

With recent approvals of long‐acting (LA) HIV pre‐exposure prophylaxis (PrEP) in the form of injectable cabotegravir and the dapivirine ring, programmes need to consider how to optimize the delivery of PrEP methods, including by leveraging lessons from the past decade of oral PrEP delivery.

Discussion

Framed around differentiated service delivery building blocks, the major considerations for the delivery of LA PrEP are how to reach the populations who would most benefit from PrEP, where to locate PrEP services, how to reduce the user burden of accessing and continuing with PrEP, and how to integrate PrEP with other services. Demand creation for LA PrEP and education about new LA PrEP options should be co‐developed with communities and be positively framed. Client‐facing clinical decision support tools provide information about HIV prevention and PrEP options in non‐technical ways and can support their informed decision‐making about PrEP. Training for providers is needed to increase their ability to ask about sexual and drug use behaviours in a non‐judgmental and comfortable manner as part of risk assessment, discuss harm reduction strategies and counsel about available PrEP options that fit clients’ circumstances and needs. PrEP adherence support should include supportive counselling and be tailored to address an individual's particular barriers and needs. Reminders through text messaging or calls can foster PrEP persistence, given the narrow the window around dosing for injectable cabotegravir. Strategies are needed to expand PrEP delivery options, including telePrEP, pharmacy‐based PrEP, key population‐led services and mobile venues. Integrated delivery models are needed which include sexually transmitted infection testing and treatment, contraception for cis‐women not desiring to become pregnant, PrEP for pregnant women in high HIV prevalence settings, and gender‐affirming hormones and support for transgender persons.

Conclusions

The outcome of expanding PrEP options through LA PrEP formulations is to increase PrEP coverage, adherence, persistence and effectiveness by offering a choice of PrEP that meets the needs of persons who would benefit from PrEP. The lessons learned from the delivery of oral PrEP about demand creation, informed client decision‐making, provider training, adherence support and service delivery model are relevant to the delivery of LA PrEP and integration with other services.
Implementation and resource needs for long‐acting PrEP in low‐ and middle‐income countries: a scoping review
Authors: Castor Delivette , Heck Craig J. , Quigee Daniela , Telrandhe Niharika Vasant , Kui Kiran , Wu Jiaxin , Glickson Elizabeth , Yohannes Kibret , Rueda Sergio Torres , Bozzani Fiammetta , Meyers Kathrine , Zucker Jason , Deacon Justine , Kripke Katharine , Sobieszczyk Magdalena E. , Terris‐Prestholt Fern , Malati Christine , Obermeyer Chris , Dam Anita , Schwartz Katie , Forsythe Steven
Published: July 2023

Introduction

Several low‐ and middle‐income countries (LMICs) are preparing to introduce long‐acting pre‐exposure prophylaxis (LAP). Amid multiple pre‐exposure prophylaxis (PrEP) options and constrained funding, decision‐makers could benefit from systematic implementation planning and aligned costs. We reviewed national costed implementation plans (CIPs) to describe relevant implementation inputs and activities (domains) for informing the costed rollout of LAP. We assessed how primary costing evidence aligned with those domains.

Methods

We conducted a rapid review of CIPs for oral PrEP and family planning (FP) to develop a consensus of implementation domains, and a scoping review across nine electronic databases for publications on PrEP costing in LMICs between January 2010 and June 2022. We extracted cost data and assessed alignment with the implementation domains and the Global Health Costing Consortium principles.

Results

We identified 15 implementation domains from four national PrEP plans and FP‐CIP template; only six were in all sources. We included 66 full‐text manuscripts, 10 reported LAP, 13 (20%) were primary cost studies‐representing seven countries, and none of the 13 included LAP. The 13 primary cost studies included PrEP commodities (n = 12), human resources (n = 11), indirect costs (n = 11), other commodities (n = 10), demand creation (n = 9) and counselling (n = 9). Few studies costed integration into non‐HIV services (n = 5), above site costs (n = 3), supply chains and logistics (n = 3) or policy and planning (n = 2), and none included the costs of target setting, health information system adaptations or implementation research. Cost units and outcomes were variable (e.g. average per person‐year).

Discussion

LAP planning will require updating HIV prevention policies, technical assistance for logistical and clinical support, expanding beyond HIV platforms, setting PrEP achievement targets overall and disaggregated by method, extensive supply chain and logistics planning and support, as well as updating health information systems to monitor multiple PrEP methods with different visit schedules. The 15 implementation domains were variable in reviewed studies. PrEP primary cost and budget data are necessary for new product introduction and should match implementation plans with financing.

Conclusions

As PrEP services expand to include LAP, decision‐makers need a framework, tools and a process to support countries in planning the systematic rollout and costing for LAP.
Effect of a multinutrient supplement as an adjunct to nonsurgical treatment of periodontitis: A randomized placebo‐controlled clinical trial
Authors: Laky Brenda , Bruckmann Corinna , Blumenschein Julian , Durstberger Gerlinde , Haririan Hady
Published: July 2023

Background

The aim of this double‐blind randomized placebo‐controlled clinical trial was to evaluate the efficacy of a multinutrient supplement as an add‐on therapy to scaling and root planing for patients with periodontitis.

Methods

Forty‐two patients with stage III or IV periodontitis were randomly allocated to a 2‐month treatment of either a multinutrient supplement containing vitamin C, vitamin E, zinc, selenium, alpha‐lipoic‐acid, cranberry extract, grapeseed extract, and coenzyme Q10 or placebo capsules as an adjunct to conservative periodontal therapy. Periodontal parameters, including probing pocket depth, gingival recession, bleeding on probing, approximal plaque index, and papillary bleeding index, were assessed. Clinical attachment loss, periodontal inflamed surface area, periodontal epithelial surface area, and percentages of pocket sites with ≤3, ≤4, ≥5, ≥6, ≥7, and ≥4 mm with bleeding on probing were calculated.

Results

All clinical parameters significantly improved from baseline to reevaluation within each group (p < 0.05). Multinutrient intake resulted in a significantly higher reduction of probing‐pocket‐depth (−0.75 ± 0.42 mm) and bleeding‐on‐probing (−21.9 ± 16.1%) from baseline to reevaluation compared with placebo (−0.51 ± 0.30 mm, p = 0.040 and −12.5 ± 9.8%, p = 0.046, respectively). All periodontal parameters showed insignificantly higher improvements in patients receiving the supplement compared with those receiving the placebo (p > 0.05).

Conclusions

Multinutrient supplementation as an adjunct to nonsurgical treatment of periodontitis showed some additional benefit regarding probing‐pocket‐depth and bleeding‐on‐probing. However, the clinical relevance needs to be further explored.
A comparison of soil liming requirement methodologies in temperate, Northern European pedo‐climates
Authors: Boyko Rose , Paton Graeme , Walker Robin , Watson Christine , Norton Gareth
Published: July 2023

Background

Liming agricultural land is essential to optimise crop yield and soil nutrients. Despite the importance of pH management in agricultural soils, liming applications have been decreasing in the United Kingdom for decades. There is no comparison of contemporary and historical liming requirement (LR) methods for Northern European, temperate climate mineral soils high in organic matter (OM).

Aims

The aims of this research were to thoroughly comparatively analyse current methodologies and to ascertain which soil characteristics contribute to LR reactions.

Methods

Analysis compared methods for determining liming values common in the United Kingdom (Scottish Agricultural College [SAC] look‐up chart, RothLime model), Europe and the United States (Shoemaker–McLean–Pratt, Sikora, Modified Mehlich buffers), and the 30‐min calcium hydroxide titration developed by the University of Georgia.

Results

RothLime and SAC highly underestimated the LR value in acidic soils. The buffers highly over or underestimated LRs. The UGA titration method is a cheap, easy and accurate method which could be utilised for high OM soils but requires further calculation development. The characteristics most associated with soil–lime reactions in this experiment were measures of exchangeability (cation exchange capacity and loss on ignition, and by proxy, lime buffering capacity).

Conclusions

There is an opportunity to create buffer calculators and titration equations adapted to high OM soils. These are suggested for further development, through a larger diversity of UK soil types grouped by buffering capacity ranges. Including soil exchangeability factors in lime management calculations may contribute to more accurate values and therefore better resource management. Increasing LR accuracy for site‐specific soil pH management, used in precision agriculture technologies, is a necessary tool for the conservation of natural resources like limestone, managing resource use efficiency, and for optimising yields.
Perceptions of pesticide use and health risks among apple growers in Kashmir Himalaya
Authors: Ashraf Moieza , Hassan Saima , Dar Shahid Ahmad
Published: July 2023

Background

Understanding the patterns of pesticide use is important in protecting the environment and farmer's health for improvement of sustainability in chemical pest control. Studies on the knowledge and awareness of pesticides by farmers are often incomplete. Therefore, our study aimed at investigating the awareness and knowledge of pesticides from a detailed survey of 394 apple growers in the Kashmir Himalaya.

Results

The study revealed that farmers have inadequate knowledge and awareness about pesticides. About 47.2% of the farmers are choosing pesticides based on the efficiency of the pest/pathogen control, 38.1% are choosing pesticides based on the cost of the product, and 14.7% of the farmers are choosing pesticides based on ease of availability. Most of the farmers rated the principles of Integrated Pest Management (IPM) as not important. The farmers believed that the use of pesticides is the only way of controlling the pest outbreaks that ultimately led to reckless spraying of pesticides. Our results revealed that farmers are spraying pesticides without protective gears and inappropriate dumping of pesticides and their containers, risking the health of humans and the environment. Almost 96% of the farmers feel burning and irritation to the eyes and skin, headache, and vomiting due to pesticide spraying. The results of this research work accentuate the requirement to educate apple growers about the adequate and safe use of pesticides to avoid risks to public and environmental health.

Conclusion

The study concludes that farmers are significantly impacted by the use of pesticides. Ineffective actions of pesticide dealers, government regulations, and illiteracy of farmers are the main causes of the reckless use of pesticides. Therefore, special attention should be paid towards sustainable approaches of pesticide spraying and use of safety gears like personal protective equipment, for protection of human and environmental health.