bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of Clinical Precision Chemotherapy by Patient‐Derived 3D Bioprinting Models of Colorectal Cancer and Its Liver Metastases
Authors: Sun Hang , Sun Lejia , Ke Xindi , Liu Lijuan , Li Changcan , Jin Bao , Wang Peipei , Jiang Zhuoran , Zhao Hong , Yang Zhiying , Sun Yongliang , Liu Jianmei , Wang Yan , Sun Minghao , Pang Mingchang , Wang Yinhan , Wu Bin , Zhao Haitao , Sang Xinting , Xing Baocai , Yang Huayu , Huang Pengyu , Mao Yilei
Published: November 2023

Methods accurately predicting the responses of colorectal cancer (CRC) and colorectal cancer liver metastasis (CRLM) to personalized chemotherapy remain limited due to tumor heterogeneity. This study introduces an innovative patient‐derived CRC and CRLM tumor model for preclinical investigation, utilizing 3d‐bioprinting (3DP) technology. Efficient construction of homogeneous in vitro 3D models of CRC/CRLM is achieved through the application of patient‐derived primary tumor cells and 3D bioprinting with bioink. Genomic and histological analyses affirm that the CRC/CRLM 3DP tumor models effectively retain parental tumor biomarkers and mutation profiles. In vitro tests evaluating chemotherapeutic drug sensitivities reveal substantial tumor heterogeneity in chemotherapy responses within the 3DP CRC/CRLM models. Furthermore, a robust correlation is evident between the drug response in the CRLM 3DP model and the clinical outcomes of neoadjuvant chemotherapy. These findings imply a significant potential for the application of patient‐derived 3DP cancer models in precision chemotherapy prediction and preclinical research for CRC/CRLM.
A Soft Continuum Robotic Arm with a Climbing Plant‐Inspired Adaptive Behavior for Minimal Sensing, Actuation, and Control Effort
Authors: Naselli Giovanna A. , Scharff Rob B. N. , Thielen Marc , Visentin Francesco , Speck Thomas , Mazzolai Barbara
Published: November 2023

A key challenge in designing soft continuum robotic arms is the realization of intelligent behavior while minimizing sensing, actuation, and control effort. This work investigates how soft continuum arms can benefit from mimicking the distribution of flexural rigidity of searcher stems in climbing plants to accomplish this goal. A modeling approach is presented to tune both the structural design and the tactile sensor design of a soft continuum arm inspired by the flexural rigidity distribution of Mandevilla cf. splendens’ searcher stems. The resulting soft continuum arm, named Mandy, can detect suitable supports along its length and twining around them using a single sensor and actuator. Through simulations and experiments, it is shown such behavior cannot be achieved with a soft continuum arm possessing uniform structural stiffness and a standard tactile sensor design. Thus, the significance of investing greater effort in structural design, leveraging biological data, to improve the design of soft continuum arms with more compact actuation and sensing hardware, is highlighted.
Pearl Memorial Lecture. Humans at the extremes: Exploring human adaptation to ecological and social stressors
Authors: Leonard William R.
Published: November 2023

The field of human biology has long explored how human populations have adapted to extreme environmental circumstances. Yet, it has become increasingly clear that conditions of social stress, poverty, and lifestyle change play equally important roles in shaping human biological variation and health. In this paper, I provide a brief background on the foundational human adaptability research of the International Biological Programme (IBP) from the 1960s, highlighting how its successes and critiques have shaped current research directions in the field. I then discuss and reflect on my own field research that has examined the influence of both environmental and social stresses on human populations living in different ecosystems: the Peruvian Andes, the Siberian arctic, and the Bolivian rainforest. Finally, I consider how the papers in this special issue advance our understanding of human adaptability to extreme conditions and offer directions for future research. Drawing on our field's distinctive evolutionary and biocultural perspectives, human biologists are uniquely positioned to examine how the interplay between social and ecological domains influences the human condition.
Prevalence and risk factors of low birth weight in the United States: An analysis of 2016–2021 data
Authors: Zheng Shimin , Cao Yan , Strasser Sheryl , Wei Holly
Published: November 2023

Background

Low birthweight (LBW), infants weighing less than 2,500 g, is a global health concern associated with high infant morbidity and mortality rates. This study investigates LBW prevalence and its relation to maternal sociodemographic characteristics and lifestyle behaviors factors in the United States (US).

Methods

This analysis used the National Survey of Children's Health (NSCH) data from 2016 to 2021, including n = 225,443 children aged 0–17 years. 18,131 had LBW (<2,500 g), and 2810 had very LBW (VLBW) (<1,500 g). Logistic regression calculated odds ratios (OR) using LBW as the dependent variable, adjusting for various factors.

Results

Between 2016 and 2021 in the United States, LBW prevalence averaged 9.31%, with VLBW at 1.50%. Mothers aged 18–35, White, had the lowest LBW (7.63%) and VLBW (1.17%) rates. Mothers aged ≤18 years, black, had the highest LBW (15.45%) and VLBW infants (4.70%). Maternal age emerged as a significant LBW factor, with an OR of 1.27 for ≤18 and 1.19 for >35. Children in poor health had the highest OR (2.87). Race/ethnicity and other disparities were observed.

Conclusion

Our study highlights LBW risk among non‐White mothers with specific criteria, emphasizing the need for continued exploration of intersectional targets for change that are exacerbating LBW disparities among marginalized populations which may be artificially attributed to biologic determinants and individual‐level risk factors. In‐depth analysis of repressive structures at the root of inequalities demand continued research on macro levels of influence. Customized healthcare reform holds the greatest potential to disrupt the patterns contributing to poor health outcomes among LBW children, and will ultimately maximize the reach and effectiveness of health promotion strategies and clinical practices aimed to improve universal maternal and infant health.
Frequency‐Scanning Considerations in Axionlike Dark Matter Spin‐Precession Experiments
Authors: Zhang Yuzhe , Tumturk Deniz Aybas , Bekker Hendrik , Budker Dmitry , Kimball Derek F. Jackson , Sushkov Alexander O. , Wickenbrock Arne
Published: November 2023

Galactic dark matter may consist of axionlike particles (ALPs) that can be described as an “ultralight bosonic field” oscillating at the ALP Compton frequency. The ALP field can be searched for using nuclear magnetic resonance (NMR), where resonant precession of spins of a polarized sample can be sensitively detected. The ALP mass to which the experiment is sensitive is scanned by sweeping the bias magnetic field. The scanning either results in detection of ALP dark matter or rules out ALP dark matter with sufficiently strong couplings to nuclear spins over the range of ALP masses corresponding to the covered span of Larmor frequencies. In this work, scanning strategies are analyzed with the goal of optimizing the parameter‐space coverage via a proper choice of experimental parameters (e.g., the effective transverse relaxation time).
Antiswelling and robust supramolecular polyurea hydrogels induced by the synergy of hydrogen bond and hydrophobic interaction for constructing durable underwater anti‐oil‐fouling coatings
Authors: Li Bengang , Tian Xin , Cao Xuzhi , Luo Zhenyang
Published: November 2023

Hydrogels are attractive materials for constructing underwater antifouling coatings on solid substrates. However, the application of hydrogel coatings usually faces the obstacles of complex preparation process and poor durability. Herein, we present a facile method to prepare durable hydrogel coatings on metal foils based on rationally designed supramolecular polyurea (PU) hydrogels. PU hydrogels are designed to be cross‐linked with hydrogen bonds (H‐bonds) and hydrophobic interactions in the hard segment domains by using dihydrazides with different alkyl spacer lengths ((CH2)m) as chain extender. The synergy of H‐bond and hydrophobic interaction can stabilize H‐bonds in water, as confirmed by Raman spectroscopy. As a result, PU hydrogels exhibit antiswelling capacity and robustness in both deionized water and seawater. Subsequently, PU hydrogel coatings on Cu/Al foils are prepared by convenient brush coating and subsequent swelling. The resulting hydrogel coatings exhibit excellent underwater anti‐oil‐adhesion and self‐cleaning property, and are durable enough to withstand various static and dynamic damaging tests. The good durability of PU hydrogel coatings should be ascribed to the robust adhesion interface and excellent antiswelling capacity of PU hydrogels. The combination of facile preparation and good durability makes PU hydrogel coatings promising candidates for reliable underwater antifouling.
Magnetic‐field‐induced Fe3O4@CNTs/PES/SPSf composite membrane for efficient removal of methylene blue by adsorption and catalytic degradation
Authors: Ji Yanhong , Zhang Ruonan , Han Zunbo , Jing Ming , Liu Xi , Cai Jiayi , He Benqiao
Published: November 2023

Novel composite membranes are successfully developed for adsorption and catalytic degradation of methylene blue (MB) by blending Fe3O4‐coated CNTs (Fe3O4@CNTs) nanoparticles in polyethersulfone (PES) and sulfonated polysulfone (SPSf) matrix via nonsolvent‐induced phase separation (NIPS) method assisted by magnetic field. Fe3O4@CNTs nanoparticles migrate to the separation layer under the induction of magnetic field, thus Fe3O4@CNTs/PES/SPSf composite membranes prepared under magnetic field exhibit a better dye removal ability compared with that without magnetic field. The MB removal ratio by Fe3O4@CNTs/PES/SPSf composite membrane containing 8 wt% Fe3O4@CNTs (M2−M) can reach up to 99% in 30 min under the conditions of 0.25 g composite membrane, 20 mg/L MB, 0.1 mol/L H2O2, pH = 3 and 80°C. Furthermore, the composite membranes show excellent recycling performance, as the MB removal capacity remains at 99% even after four cycles.
Auswirkungen von Verkehrserschütterungen auf jungen Beton: Teil 1
Authors: Gasser Christian , Hausner Lukas , Vorwagner Alois , Klackl Stefanie , Manninger Tanja , Krispel Stefan
Published: November 2023

Im Forschungsprojekt COUNT (Concreting under traffic) werden die Auswirkungen von Verkehrserschütterungen auf jungen Beton umfangreich untersucht. Diese Fragestellung hat in letzter Zeit an Relevanz gewonnen. Bei Erneuerungs‐ oder Erweiterungsarbeiten an Brücken müssen oft Verkehrssperren verhängt werden, da man fürchtet, dass die vom Verkehr verursachten Erschütterungen den jungen (aushärtenden) Beton schädigen. COUNT zielt darauf ab, kritische Erschütterungswerte und zugrunde liegende Schädigungsmechanismen anhand von drei Versuchsserien zu ermitteln. Dabei werden sowohl harmonische als auch reale Brückenschwingungen infolge von Zug‐, Lkw‐ und Pkw‐Verkehr angewendet und es werden die Auswirkungen auf sowohl den Werkstoff Beton selbst, als auch auf das Verbundverhalten zwischen Beton und Bewehrung sowie den Kontakt zwischen bestehenden und neuen Betonteilen untersucht. Im vorliegenden ersten Teil des Aufsatzes wird über die Ergebnisse der Versuchsserien 1 und 2 berichtet, bei welchen Kleinkörper während der Erhärtung systematisch durch künstliche Schwingungen angeregt wurden. Dabei wurde festgestellt, dass herkömmliche Verkehrserschütterungen die Festigkeit von Beton an sich nicht beeinträchtigen, jedoch der Verbund zwischen Beton und Bewehrung geschwächt werden kann, wenn die Erschütterungen zu groß sind. Außerdem wurde herausgefunden, dass (differentielle) Verschiebungen sich besser als Beurteilungsgröße eignen als die Schwinggeschwindigkeit.
Brentuximab vedotin in treating Chinese patients with lymphoma: A multicenter, real‐world study
Authors: Zhang Xudong , Qiao Honghan , Chai Xiaofei , Gao Xue , Ma Rongjun , Li Yufu , Zhu Zunmin , Zhang Mingzhi
Published: November 2023

Background

Brentuximab vedotin (BV) was approved as a therapy for patients with CD30‐positive lymphoma in China in 2020 based on the results of multiple clinical trails. Few Chinese real‐world data of its use are yet available. Herein, we present the application situation of BV in patients with lymphoma among different hospitals in Henan province in China under real‐world conditions.

Methods

This was a multicenter and retrospective study in 104 patients with lymphoma who received BV for the first time between August 2020 and September 2022 across eight centers in Henan province. Data on the clinical use, effectiveness and adverse events (AEs) of BV were extracted from patient medical records. Short‐term effectiveness was assessed based on objective response rate (ORR), complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Progression‐free survival (PFS) and overall survival (OS) were calculated using Kaplan–Meier method. Safety was also evaluated in our study.

Results

104 lymphoma patients were enrolled in our study, who had completed a median of two cycles (range,1–8) of BV‐based treatment. A total of 72.1% of patients were relapsed/refractory (R/R) lymphoma, and only 27.9% were previously untreated lymphoma who received BV in frontline treatment settings. Among them who received effectiveness evaluation, the ORR achieved 64.5% (CR 25.8%, PR 38.7%). After a median follow‐up of 11 months, the 6‐month PFS rate and OS rate achieved 77.2% and 90.1% respectively, and the 12‐month PFS rate and OS rate achieved 77.2% and 79.9% respectively. In general, BV‐based treatment was well‐tolerated, with 38.5% incidence of grade ≥3 AEs. The most commonly reported AEs were hematologic disorders, especially neutropenia, with the incidence reaching 50.0%.

Conclusions

BV‐based regimens could be a promising therapeutic option with remarkable effectiveness and moderate toxicity in treating Chinese lymphoma patients with CD30 expression.
Efficacy of a patient with scar constitution combined with corrosive esophageal strictures after different endoscopic therapies
Authors: Wang Haixia , Tao Wei
Published: November 2023

Key Clinical Message

Oral corrosive substances can cause esophageal or gastrointestinal strictures, leading to malnutrition and gastrointestinal dysfunction, directly affecting the patients' quality of life. The aim of the case was to compare the efficacy of different endoscopic therapy methods.
Coronary‐cameral fistula in an infant patient: An incidental diagnosis
Authors: Velázquez‐Castañeda Raúl , De La Puente‐Tawil Ilana , Molina‐Castillo Sofía , Proaño‐Bernal Leonardo , Rodríguez‐Salazar Mariell Alejandra , Masso‐Bueso Steve , Alexanderson‐Rosas Erick , Arenas‐Fabbri Vincenzo
Published: November 2023

Key Clinical Message

Coronary artery fistula is a rare abnormal connection between the heart arteries. Patients may remain asymptomatic until adulthood, potentially experiencing life‐threatening complications. Adequate monitoring and therapeutic management are essential.
Surgical orthodontic intervention for impacted maxillary permanent central incisors: A case series
Authors: Jha Kanistika , Adhikari Manoj
Published: November 2023

Key Clinical Message

Impacted maxillary central incisors represent a relatively infrequent occurrence. This condition significantly impacts the patient's self‐esteem and aesthetic concerns. Effective resolution is achievable through a combined strategy involving surgical exposure, bracket attachment, and subsequent orthodontic extrusion. The Surgical orthodontic approach is the optimal strategy for addressing impacted maxillary central incisors.

Central incisor is rarely impacted teeth often associated with supernumerary teeth. This case series includes three cases of central incisor impaction presented with complaints of missing teeth, unesthetic appearance, and unclear speech. All the cases were managed with surgical exposure followed by traction by orthodontic force, restoring smile aesthetics.
Clinical response to therapeutic plasmapheresis and intravenous immunoglobulin in pregnancies complicated by alloimmunization despite persistently high titers: Report of two cases
Authors: Bahkali Nedaa , Alhawsawi Ebtihal , Althakafi Kholoud , Arab Kholoud , Rayes Almotasimbellah , Badawi Maha A.
Published: November 2023

Key Clinical Message

Plasmapheresis and IVIG use in cases of alloimmunization during pregnancy are effective strategies when severe early fetal anemia is anticipated. Despite no change in antibody titer levels before and after plasmapheresis, clinical response was observed in both fetuses, and both had an excellent obstetrical outcome.

Hemolytic disease of the fetus and newborn is a potentially lethal complication of alloimmunization, and intrauterine fetal blood transfusion (IUBT) is the standard treatment and care plan for severe fetal anemia. However, IUBT is technically unattainable before 20 weeks of gestation. Plasmapheresis and intravenous immunoglobulin (IVIG) are the two treatment modalities described in the literature that postpone the need for transfusion until after 20 weeks. Here, we present two cases of alloimmunization (one with anti‐Kell and the other with anti‐D). Both had poor outcomes in previous pregnancies because of the early development of severe fetal anemia and hydrops before 24 weeks of gestation. Both patients underwent three sessions of plasmapheresis before 18 weeks, followed by weekly IVIG infusion, which continued until 23–27 weeks of pregnancy. Antibody titers were measured before and after plasmapheresis. In addition, weekly MCA Doppler was performed to monitor the development of severe fetal anemia requiring blood transfusion, which was diagnosed when the peak systolic velocity (PSV) was 1.5 multiples of the median or more. The first patient underwent IUBT at 24 weeks and the second at 28 weeks, as indicated by the MCA Doppler. Both patients were delivered by cesarean section, the first at 34 weeks and the second at 36 weeks, for different obstetrical indications. Both pregnancies resulted in a live birth. We conclude that the use of plasmapheresis and IVIG in alloimmunization during pregnancy is an effective treatment strategy when severe early fetal anemia is anticipated before 20 weeks of gestation. Despite no change in antibody titer levels before and after plasmapheresis, a clinical response was observed in both fetuses, and both had excellent obstetrical outcomes.
Living with chronic progressive external ophthalmoplegia alongside cataract, peptic ulcer disease, diabetes and hypertension in Ghana
Authors: Boi‐Dsane Naa Adzoa Adzeley , Seidu Anwar Sadat , Simon Judith , Bonsaana Gilbert Batieka
Published: November 2023

Key Clinical Message

This is the case of a 51‐year‐old woman with chronic progressive external ophthalmoplegia (CPEO) alongside some comorbidities in a low‐resource setting. This report seeks to sensitise clinicians about this rare condition in order to increase their index of suspicion and avoid misdiagnosis.
A rare case with melatonin‐induced on top of alcohol intoxication Brugada type 2 pattern
Authors: Hassan Muad Abdi , Arbab Fatima Khalid , Alsakaji Obada Adel , Dulli Ahmad , Abdow Mohammad Abdow , Ullah Fatima Moulana Mohammed Jamal , Wali Irfan Ullah
Published: November 2023

Key Clinical Message

Brugada syndrome (BrS), a genetically inherited ion channelopathy, has been linked to a considerable number of unexplained sudden cardiac deaths in patients without structural heart defects, and Brugada phenocopy (BrP) is a condition where there is an identical electrocardiogram (ECG) pattern to a congenital BrS, but this is due to other reversible etiologies. A 37‐year‐old male patient with a documented history of hypertension presented with vomiting after taking 43, 10 mg, melatonin pills and binge drinking locally made alcohol 2 days before. ECG showed right ventricular conduction delay with a “saddleback” appearance, with the J point elevated more than 2 mm and the terminal portion of the ST‐segment elevated more than 1 mm in leads V1 and/or V2. Which returned to normal after a few hours. The association between the use of melatonin and the finding of the Brugada pattern (BP) in a patient with normal heart structure or abnormal ECGs has been documented in much literature, and although no official melatonin dosage is recommended for adults, melatonin has been reported to cause and protect from arrhythmias through different mechanisms. In our patient, after alcohol intoxication was ruled out as a cause, melatonin was the only significant risk factor related to his ECG findings. The BP can be found in patients with otherwise normal heart structure and ECG records, and an overdose of melatonin, which is used as an over‐the‐counter sleep medication, was found to be a possible cause of finding this pattern in these patients after excluding other known causes.
Controlling the Coke Formation in Dehydrogenation of Propane by Adding Nickel to Supported Gallium Oxide
Authors: Baumgarten Robert , Ingale Piyush , Ebert Fabian , Mazheika Aliaksei , Gioria Esteban , Trapp Katharina , Profita Kevin D. , Naumann d'Alnoncourt Raoul , Driess Matthias , Rosowski Frank
Published: November 2023

Atomic layer deposition was applied on mesoporous silica to synthesize a highly dispersed gallium oxide catalyst. This system was used as starting material to investigate different loadings of nickel in the dehydrogenation of propane under industrially relevant, Oleflex‐like conditions. The formation of NiGa alloys was confirmed by X‐ray diffraction analysis and electron microscopy. Surprisingly, the nanoalloys enhanced the selectivity towards C3H6 while decreasing the tendency for coking. Herein, in situ thermogravimetry, and measured mass fractions of carbon revealed that the coking rate was reduced by over 50 % compared to the pristine gallium oxide. Generally, the increased selectivity can be explained by the partial hydrogenation and reduction of the gallium oxide surface. The optimum temperature for the removal of deposited carbon was evaluated by a temperature programmed oxidation. Finally, the best‐performing Ni−GaOx catalyst was employed in a cycled experiment with periodic reaction and regeneration tests. After regeneration, the selected Ni−GaOx catalyst provided a higher yield of propylene compared to the unmodified gallium oxide.
Impact of Built‐in Helical Fins on the Performance of Oil‐Gas Cyclone Separators
Authors: Fu Zeming , Wu Huagen , Liang Mengtao , Guo Zhendong , Hou Liang , Xing Ziwen
Published: November 2023

An improved design was proposed by incorporating helical fins onto the vortex finder, and the impact on the comprehensive performance of the oil‐gas cyclone separator was analyzed based on flow field characteristics. The results revealed that the integration of helical fins led to a slight enhancement in the overall separation efficiency and a significant reduction in pressure drop, thus contributing to the decrease of energy consumption in industrial processes. The orthogonal experimental design (OED) method was utilized for the discussion and optimization of five structural parameters related to the helical fins. This study provides new insights for the design of internal components of oil‐gas separators.
Collective Effects of Multiple Fluorine Atoms Causing π‐philic Characteristic within a Caged Polyoxometalate Framework
Authors: Murata Chinatsu , Nakashuku Akari , Shichibu Yukatsu , Konishi Katsuaki
Published: November 2023

Perfluorination brings about distinctive properties arising from the unusual nature of the F element, which have been extensively developed in materials science and chemistry. Herein we report that the construction of F‐rich inner space within a hollowed Mo132O372 cage ([Mo132O372(OCOR)30(H2O)72]42−) leads to the emergence of unique guest binding activities in encapsulation. Prominently, the trifluoroacetate‐modified cage (R=CF3, 2) having as many as 90 F groups inside favors trapping cyclopentadiene (Cp), which is hardly trapped by the non‐fluorinated counterpart (R=CH3, 1). Systematic studies using related hydrocarbons show that the amount of the encapsulated guest is correlated with the unsaturation degree of the guests, implying the involvement of the attractive interaction of the CF3‐modified interior wall with the guest π‐electron clouds. Control experiments using the semi‐fluorinated analogues (R=CF2H, CFH2) reveal that the perfluorination is a critical factor to facilitate the Cp encapsulation by 2, indicating that collective effects of polar C−F bonds spreading over the interior surface, rather than the polarity of the individual C−F bonds, are responsible. We also provide a successful example of the physical molecular confinement within the cage through the “ship‐in‐a‐bottle” Diels‐Alder reaction between trapped diene and dienophile.
π‐Electron Fluctuation‐Induced P+/C− Ambiphilic Interaction for Intramolecular CAr−H Bond Activation
Authors: Chen Jianzhou , Wang Junjian , Wang Xinghua , Wei Donghui , Duan Zheng
Published: November 2023

Herein, we describe how computational mechanistic understanding has led directly to the discovery of new 2H‐phosphindole for C−CAr bond activation and dearomatization reaction. We uncover an unexpected intramolecular C−H bond activation with a 2H‐phosphindole derivative. This new intriguing experimental observation and further theoretical studies led to an extension of the reaction mechanism with 2H‐phosphindole. Through DFT calculations, we confirm that within a five‐membered ring, the polarizable PC3 unit orchestrates the formation of an electrophilic phosphorus atom (P+) and a nucleophilic carbon atom (C−). This kinetically accessible ambiphilic phosphorus/carbon couple is spatially separated by geometric constraints, and their reactivity is modulated through structural resonance.
Research on promoting the asymmetric reaction of phenylacetylene with aldehydes by chloramphenicol base ligands
Authors: Lu Baozhao , Zhang Ruifeng , Chen Congdi , Jin Liming , Xu Jiaqi , Yang Hongjun
Published: November 2023

A series of chiral ligands were synthesized using chloramphenicol base as starting materials. These ligands were applied to the asymmetric catalytic reactions of terminal alkynes with aldehydes to obtain a propargyl alcohol product in high yield (80–94%) with excellent enantioselectivities (82–96%).
Investigating the role of genetic variation in vgll3 and six6 in the domestication of gilthead seabream (Sparus aurata Linnaeus) and European seabass (Dicentrarchus labrax Linnaeus)
Authors: Moulistanos Aristotelis , Nikolaou Theopisti , Sismanoglou Smaragda , Gkagkavouzis Konstantinos , Karaiskou Nikoleta , Antonopoulou Efthimia , Triantafyllidis Alexandros , Papakostas Spiros
Published: November 2023

Gene function conservation is crucial in molecular ecology, especially for key traits like growth and maturation in teleost fish. The vgll3 and six6 genes are known to influence age‐at‐maturity in Atlantic salmon, but their impact on other fish species is poorly understood. Here, we investigated the association of vgll3 and six6 in the domestication of gilthead seabream and European seabass, both undergoing selective breeding for growth‐related traits in the Mediterranean. We analysed two different sets of samples using two different genotyping approaches. The first dataset comprised farmed and wild populations from Greece, genotyped for SNPs within the two genes (‘gene‐level genotyping’). The second dataset examined 300–600 k SNPs located in the chromosomes of the two genes, derived from a meta‐analysis of a Pool‐Seq experiment involving farmed and wild populations distributed widely across the Mediterranean (‘chromosome‐level genotyping’). The gene‐level analysis revealed a statistically significant allele frequency differences between farmed and wild populations on both genes in each species. This finding was partially supported by the chromosome‐level analysis, identifying highly differentiated regions may be involved in the domestication process at varying distances from the candidate genes. Noteworthy genomic features were found, such as a CpG island in gilthead seabream and novel candidate genes in European seabass, warranting further investigation. These findings support a putative role of vgll3 and six6 in the maturation and growth of gilthead seabream and European seabass, emphasizing the need for further research on their conserved function.
Cheaters among pollinators: Nectar robbing and thieving vary spatiotemporally with floral traits in Afrotropical forests
Authors: Sakhalkar Sailee P. , Janeček Štěpán , Klomberg Yannick , Mertens Jan E. J. , Hodeček Jiří , Tropek Robert
Published: November 2023

Nectar robbers and thieves are common antagonists in plant–pollinator communities, where they deplete nectar without pollinating flowers, substantially affecting plant reproduction. Nevertheless, little is known about the relative abundance of such nectar exploiters in communities, even though spatiotemporal changes in the frequencies of antagonists and mutualists can exert opposing selection pressures on the traits of the interacting species. Although these effects are highly dependent on the community context, interspecific interactions have almost exclusively been studied in interacting species pairs or single‐plant studies. We hypothesized that flowers might experience a trade‐off between filtering out robbers and thieves. We used an extensive dataset of video‐recorded flower–visitor interactions along a complete elevational gradient in wet and dry seasons on Mount Cameroon to assess spatiotemporal changes in robbing and thieving associated with several floral traits. Of the 14,391 recorded visits, ~4.3% were from robbers (mostly bees and birds) and ~2.1% were from thieves (mostly flies, bees, and moths). Only 29 and 39 of the 194 studied plants were robbed and thieved, respectively. We found that specialized floral traits that prevented thieving (such as long floral tubes or spurs) made flowers susceptible to robbing, and vice versa. Cheating behavior was most frequent at mid‐elevations, with more frequent robbing during the wet season and thieving during the dry season. These trends were linked to the local floral trait composition and the associations of cheating groups with specific floral traits. Our results suggest that the roles of antagonists and mutualists in shaping partner traits may vary across communities and that they deserve more attention in future studies of interspecific interactions.
A novel endoscopic nasopharyngectomy by low‐temperature plasma radiofrequency ablation in localized recurrent nasopharyngeal carcinoma
Authors: Zou Xiong , Feng Zheng‐Kai , Hua Yi‐Jun , Liu You‐Ping , Xie Yu‐Long , Ouyang Yan‐Feng , Liu Yong‐Long , Wang Zhi‐Qiang , You Rui , Ding Xi , Yang Qi , Yu Zi‐Kun , Huang Pei‐Yu , Wang Shun‐Lan , Chen Ming‐Yuan
Published: November 2023

Objective

Endoscopic nasopharyngectomy (ENPG) with en bloc resection has been well accepted in resectable localized recurrent nasopharyngeal carcinoma (rNPC), but it is a difficult technique to master for most otorhinolaryngology head and neck surgeons. Ablation surgery is a new and simplified method to remove tumors. We designed a novel method using low‐temperature plasma radiofrequency ablation (LPRA) and evaluated the survival benefit.

Methods

A total of 56 localized rNPC patients were explained in detail and retrospectively analyzed. The surgery method was ablated from the resection margin to the center of the tumor. The postmetastatic overall survival (OS), local relapse‐free survival (LRFS) rate, progression‐free survival (PFS) and distant metastasis‐free survival (DMFS) were analyzed using the Kaplan–Meier method and compared by the log‐rank test.

Results

All surgeries were successfully performed without any severe postoperative complications or deaths. The median operation time of ablation and harvested NSFF respectively were 29 min (range, 15–100 min) and 101 min (range, 30–180 min). The average number of hospital days postoperation was 3 days (range, 2–5 days). All cases (100.0%) had radical ablation with negative resection margins. The nasopharyngeal defects were completely re‐epithelialized in 54 (96.4%) patients. As of the data cutoff (September 3, 2023), the median follow‐up time was 44.3 months (range, 17.1–52.7 months, 95% CI: 40.4–48.2). The 3‐year OS, LRFS, PFS and DMFS of the entire cohort were 92.9% (95% CI: 0.862–0.996), 89.3% (95% CI: 0.813–0.973), 87.5% (95% CI: 0.789–0.961), and 92.9% (95% CI: 0.862–0.996), respectively. Cycles of radiotherapy were independent risk factors for OS (p = 0.003; HR, 32.041; 95% CI: 3.365–305.064), LRFS (p = 0.002; HR, 10.762; 95% CI: 2.440–47.459), PFS (p = 0.004; HR, 7.457; 95% CI: 1.925–28.877), and DMFS (p = 0.002; HR, 34.776; 95% CI: 3.806–317.799).

Conclusion

Radical endoscopic nasopharyngectomy by using low‐temperature plasma radiofrequency ablation is a novel, safe and simplified method to master and disseminate for treating resectable rNPC. However, further data and longer follow‐up time are needed to prove its efficacy.
Scalable Preparation of 1‐Aminoethyl Oxindoles From Simple Benzaldehydes
Authors: Bürki Cédric , Diethelm Stefan , D'Aiuto Fabio , Künzli Marco , Mathieu Gaëlle , Schmitt Christine
Published: November 2023

Oxindoles are prevalent structures in natural products and pharmaceutically active molecules. To support structure–activity‐relationship (SAR) studies in a medicinal chemistry program, we developed a straightforward and scalable synthesis route to 1‐aminoethyl oxindole building blocks harboring various types of substituents. Our strategy relies on an intramolecular Buchwald–Hartwig amidation of a 2‐bromophenylacetic amide precursor. The cyclization substrates can be prepared from readily available benzaldehydes by ortho‐selective C(sp2)−H bromination followed by homologation to the corresponding phenylacetic acid derivatives. The process was optimized to allow for preparation of 246 g of one representative example.
Systems archetypes to investigate the unintended consequences of telehealth in rural Australia: A systems thinking approach to telehealth evaluation and policymaking
Authors: Osman Sagda , Churruca Kate , Ellis Louise A. , Braithwaite Jeffrey
Published: November 2023

As an alternative model of delivery to standard care, telehealth offers a promising solution to health access issues faced by rural and remote communities in Australia and worldwide. However, research typically focuses on its expected benefits and pitfalls, with little to no consideration of its unintended consequences and factors influencing its better utilisation. Drawing on systems thinking and informed by complexity science, we propose using systems archetypes—systems thinking tools ‐ as a magnifying lens to investigate potential telehealth unintended consequences or outcomes. We conceptualise telehealth implementation in rural and remote Australia as a sociotechnical system whereby the interactions between its various agents shape telehealth implementation and, in turn, are shaped by it. When introducing new policies or interventions to any system, these interactions often lead to outcomes other than those initially planned or intended. Although systems archetypes cannot necessarily predict these outcomes, they are valuable for helping anticipate unintended, unforeseen outcomes and facilitating discussions about them to mitigate their negative impact and maximise their benefits. Outcomes are not necessarily adverse; they can also be positive. So, investigating such outcomes will minimise their negative impact and maximise their benefit. Our method was to review existing research and a selection of complexity and systems informed frameworks. Then, we assessed systems archetypes. And how they can be utilised to investigate unintended consequences. A worked example of what an unintended consequence in the implementation of telehealth in rural and remote Australia is presented.
Improved GAN for image resolution enhancement using ViT for breast cancer detection
Authors: Rautela Kamakshi , Kumar Dinesh , Kumar Vijay
Published: November 2023

Breast cancer has a significant mortality rate and is widespread among women. Detecting it early is crucial for effective treatment. While mammograms provide detailed anatomical visuals, their accuracy is hindered by low sensitivity and high background noise, especially in dense breast tissue. This study introduces a new network architecture integrating generative adversarial networks (GANs) and vision transformers to improve reference‐based super‐resolution. The proposed model combines image generation and classification in a unified framework, eliminating the need for a separate classifier during training. To enhance GAN robustness, a unique two‐channel approach is employed, and transformer and residual learning techniques improve overall efficiency. The study introduces a novel synthetic image‐based model to improve feature detection for breast cancer classification. The proposed model shows the ability to understand information variability across different representations, enhancing accuracy and reducing computational time. Using the INbreast dataset, the results indicate the model's capability to generate high‐quality images with sensitivity and accuracy values of 0.932 and 0.988, respectively.
Deleted in Azoospermia Associated Protein 1 Shuttles Between Nucleus and Cytoplasm During Normal Germ Cell Maturation
Authors: VERA YANIRA , DAI TIANE , HIKIM AMIYA P. SINHA , LUE YANHE , SALIDO EDUARDO C. , SWERDLOFF RONALD S. , YEN PAULINE H.
Published: November 2023

DAZAP1 (Deleted in Azoospermia Associated Protein 1) was originally identified through its interaction with a putative male azoospermia factor, DAZ (Deleted in Azoospermia). It contains 2 RNA‐binding domains (RBDs) and a proline‐rich C‐terminal portion and is expressed most abundantly in testes. We used RNA in situ hybridization and immunocytochemistry to study the expression of Dazap1 in mouse testes. Dazap1 messenger RNA (mRNA) was present predominantly in immature germ cells, between the intermediate spermatogonia and preleptotene spermatocyte stages. The DAZAP1 protein was more abundant in germ cells of later stages of development and showed a dynamic subcellular distribution. High expression of DAZAP1 was first detected in midpachytene spermatocytes in stage VII tubules. In these cells, DAZAP1 was present in both the cytoplasm and the nuclei and was clearly excluded from the sex vesicles. In round spermatids, DAZAP1 was localized mainly in the nuclei, whereas in elongated spermatids, it redistributed to the cytoplasm. The subcellular distribution of DAZAP1 suggests that it shuttles between the nucleus and the cytoplasm and may play a role in mRNA transport and/or localization.
Transitory Activation and Improved Transition from Erosion to Formation within Intracortical Bone Remodeling in Hypoparathyroid Patients Treated with rhPTH(1–84)
Authors: van Dijk Christiansen Pernille , Sikjær Tanja , Andreasen Christina Møller , Thomsen Jesper Skovhus , Brüel Annemarie , Hauge Ellen Margrethe , Delaisse Jean‐Marie , Rejnmark Lars , Andersen Thomas Levin
Published: November 2023

In hypoparathyroidism, lack of parathyroid hormone (PTH) leads to low calcium levels and decreased bone remodeling. Treatment with recombinant human PTH (rhPTH) may normalize bone turnover. This study aimed to investigate whether rhPTH(1–84) continued to activate intracortical bone remodeling after 30 months and promoted the transition from erosion to formation and whether this effect was transitory when rhPTH(1–84) was discontinued. Cortical histomorphometry was performed on 60 bone biopsies from patients (aged 31 to 78 years) with chronic hypoparathyroidism randomized to either 100 μg rhPTH(1–84) a day (n = 21) (PTH) or similar placebo (n = 21) (PLB) for 6 months as add‐on to conventional therapy. This was followed by an open‐label extension, where patients extended their rhPTH(1–84) (PTH) (n = 5), continued conventional treatment (CON) (n = 5), or withdrew from rhPTH(1–84) and resumed conventional therapy (PTHw) for an additional 24 months (n = 8). Bone biopsies were collected at months 6 (n = 42) and 30 (n = 18). After 6 and 30 months, the overall cortical microarchitecture (cortical porosity, thickness, pore density, and mean pore diameter) in the PTH group did not differ from that of the PLB/CON and PTHw groups. Still, the PTH group had a significantly and persistently higher percentage of pores undergoing remodeling than the PLB/CON groups. A significantly higher percentage of these pores was undergoing bone formation in the PTH compared with the PLB/CON groups, whereas the percentage of pores with erosion only was not different. This resulted in a shift in the ratio between formative and eroded pores, reflecting a faster transition from erosion to formation in the PTH‐treated patients. In the rhPTH(1–84) withdrawal group PTHw, the latter effects of PTH were completely reversed in comparison to those of the PLB/CON groups. In conclusion, rhPTH(1–84) replacement therapy in hypoparathyroidism patients promotes intracortical remodeling and its transition from erosion to formation without affecting the overall cortical microstructure. The effect persists for at least 30 months and is reversible when treatment is withdrawn. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Utility and Limitations of TALLYHO/JngJ as a Model for Type 2 Diabetes–Induced Bone Disease
Authors: Emini Lejla , Salbach‐Hirsch Juliane , Krug Johannes , Jähn‐Rickert Katharina , Busse Björn , Rauner Martina , Hofbauer Lorenz C.
Published: November 2023

Type 2 diabetes mellitus (T2DM) increases risk of fractures due to bone microstructural and material deficits, though the mechanisms remain unclear. Preclinical models mimicking diabetic bone disease are required to further understand its pathogenesis. The TALLYHO/JngJ (TH) mouse is a polygenic model recapitulating adolescent‐onset T2DM in humans. Due to incomplete penetrance of the phenotype ~25% of male TH mice never develop hyperglycemia, providing a strain‐matched nondiabetic control. We performed a comprehensive characterization of the metabolic and skeletal phenotype of diabetic TH mice and compared them to either their nondiabetic TH controls or the recommended SWR/J controls to evaluate their suitability to study diabetic bone disease in humans. Compared to both controls, male TH mice with T2DM exhibited higher blood glucose levels, weight along with impaired glucose tolerance and insulin sensitivity. TH mice with/without T2DM displayed higher cortical bone parameters and lower trabecular bone parameters in the femurs and vertebrae compared to SWR/J. The mechanical properties remained unchanged for all three groups except for a low‐energy failure in TH mice with T2DM only compared to SWR/J. Histomorphometry analyses only revealed higher number of osteoclasts and osteocytes for SWR/J compared to both groups of TH. Bone turnover markers procollagen type 1 N‐terminal propeptide (P1NP) and tartrate‐resistant acid phosphatase (TRAP) were low for both groups of TH mice compared to SWR/J. Silver nitrate staining of the femurs revealed low number of osteocyte lacunar and dendrites in TH mice with T2DM. Three‐dimensional assessment showed reduced lacunar parameters in trabecular and cortical bone. Notably, osteocyte morphology changed in TH mice with T2DM compared to SWR/J. In summary, our study highlights the utility of the TH mouse to study T2DM, but not necessarily T2DM‐induced bone disease, as there were no differences in bone strength and bone cell parameters between diabetic and non‐diabetic TH mice. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Future Frontiers: Exploration of practices, challenges, and educational needs of genetic counselors in emerging subspecialties
Authors: Ahimaz Priyanka , Ross Meredith , Foltz Jennah , Sebastin Monisha , Naik Ketki , Kramer Tamar , Bogyo Kelsie , Primiano Michelle
Published: November 2023

The augmented use of genomic testing across different medical subspecialties has led to increased involvement of genetic counselors (GCs) in specialized areas of medicine. However, the lack of educational infrastructure required for changing scholastic needs of GCs entering new subspecialties lends to the burden of self‐directed learning and inconsistent knowledge. We conducted a cross‐sectional study surveying GCs with experience in the emerging genetic subspecialties of Immunology, Dermatology, Endocrinology, and Pulmonology (abbreviated as “IDEP”) on current practices, clinical challenges, and educational strategies undertaken while working in these settings. We compared knowledge and confidence in skills related to IDEP patient care between GCs who do (experienced cohort) and do not (control cohort) practice in these settings to assess their comfort with working in subspecialties. Participants were recruited from the National Society of Genetic Counselors membership. A total of 304 GCs (178 experienced and 126 control) completed the survey. Most GCs in the experienced cohort saw IDEP patients by themselves (n = 104; 58.4%) or with a geneticist (n = 97; 54.4%) and almost all (n = 176; 99%) cited GeneReviews as a primary informational source for IDEP genetics but half (n = 91; 51.1%) agreed that a dedicated online course would be the best way to learn about a specific subspecialty. The experienced cohort scored higher on confidence in all skills (p < 0.001, z = 7.32) and knowledge (p < 0.001, z = 5.68) related to IDEP genetics than the control cohort. Previous exposure to IDEP through graduate school coursework and rotations positively correlated with better self‐confidence in skills (p = 0.02, z = −2.19; p < 0.001, z = −5.25) and genetic knowledge (p = 0.03, z = −2.09; p < 0.001, z = −2.81) related to IDEP patient care. Years of experience working as a GC did not correlate with better confidence in skills (p = 0.53) or better IDEP genetic knowledge (p = 0.15). Our findings show that provision of opportunities for increased exposure to subspecialties could help maximize GCs' ability to work in emerging niche fields.