bluuebunny/crossref_metadata_2025 huggingface dataset:
The antianxiety effects of koumine and gelsemine, two main active components in the traditional Chinese herbal medicine Gelsemium: A comprehensive review
Authors: Long Jiangyu , Tang Mohuan , Zuo Mengting , Xu Wenbo , Meng Siyu , Liu Zhaoying
Published: December 2023

The genus Gelsemium belongs to the family Loganiaceae, one of the traditional Chinese herbs. Gelsemium is traditionally used to treat rheumatoid and neuropathic pain. Its root extracts were found to protect against anxiety, especially the alkaloids koumine and gelsemine. Indeed, koumine and gelsemine can act as positive agonists of the glycine receptor (GlyR), which reduces neuronal excitability through chloride influx and can also increase neuroactive steroid content by enhancing 3alpha‐hydroxysteroid oxidoreductase (3α‐HSOR) expression. The latter can activate the excitation‐inhibitory response via the γ‐aminobutyric acid type A receptor (GABAAR), reduce the abnormal corticotropin‐releasing hormone (CRH) increase in the hypothalamus, inhibit adrenocorticotropic hormone (ACTH) secretion, and effectively inhibit the abnormal ACTH and corticosterone increases in the circulation. In addition, koumine and gelsemine inhibited the expression of the NLR family pyrin domain containing 3 (NLRP3) inflammasome, inhibiting the release of inflammatory factors and regulating anxiety‐related neural circuits. Gelsemine also inhibited the overexpression of brain‐derived neurotrophic factor (BDNF) and cAMP response element‐binding protein (CREB) in the hypothalamus to maintain the plasticity of brain neurons and protect neurogenesis to achieve anxiety regulation. In general, this article reviews the recent studies on Gelsemium in the anxiety field, discusses its possible antianxiety mechanism, and confirms the potential of Gelsemium as a therapeutic drug for anxiety‐related diseases.
Advances in the treatment of IgA nephropathy with biological agents
Authors: Zhuang Yongze , Lu Hailing , Li Junxia
Published: December 2023

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerular disease, and the “four‐hit” theory represents its currently accepted pathogenic mechanism. Mucosal immunity triggered by infections in the respiratory tract, intestines, or other areas leads to antigen presentation, T cell stimulation, B cell maturation, and the production of IgA‐producing plasma cells. The proteins B‐lymphocyte stimulator (BLyS) and a proliferation‐inducing ligand (APRIL) are involved in this process, and alternative complement and lectin pathway activation are also part of the pathogenic mechanism. Kidney Disease Improving Global Outcomes guidelines indicate that a specific effective treatment for IgAN is lacking, with renin–angiotensin–aldosterone system inhibitors being the primary therapy. Recent research shows that biological agents can significantly reduce proteinuria, stabilize the estimated glomerular filtration rate, and reverse some pathological changes, such as endocapillary proliferation and crescent formation. There are four main categories of biological agents used to treat IgA nephropathy, specifically anti‐CD20 monoclonal antibodies, anti‐BLyS or APRIL monoclonal antibodies, monoclonal antibodies targeting both BLyS and APRIL (telitacicept and atacicept), and monoclonal antibodies inhibiting complement system activation (narsoplimab and eculizumab). However, further research on the dosages, treatment duration, long‐term efficacy, and safety of these biological agents is required.
Tau and neurodegeneration
Authors: Goedert Michel , Crowther R. Anthony , Scheres Sjors H. W. , Spillantini Maria Grazia
Published: December 2023

First identified in 1975, tau was implicated in Alzheimer's disease 10 years later. Filamentous tangle inclusions were known to be made of hyperphosphorylated tau by 1991, with similar inclusions gaining recognition for being associated with other neurodegenerative diseases. In 1998, mutations in MAPT, the gene that encodes tau, were identified as the cause of a dominantly inherited form of frontotemporal dementia with abundant filamentous tau inclusions. While this result indicated that assembly of tau into aberrant filaments is sufficient to drive neurodegeneration and dementia, most cases of tauopathy are sporadic. More recent work in experimental systems showed that filamentous assemblies of tau may first form in one brain area, and then spread to others in a prion‐like fashion. Beginning in 2017, work on human brains using high‐resolution techniques has led to a structure‐based classification of tauopathies, which has opened the door to a better understanding of the significance of tau filament formation.
Population‐Based Characterization of the Pharmacokinetics and Food Effect of ANAVEX3‐71, a Novel Sigma‐1 Receptor and Allosteric M1 Muscarinic Receptor Agonist in Development for Treatment of Frontotemporal Dementia, Schizophrenia, and Alzheimer Disease
Authors: Fadiran Emmanuel O. , Hammond Edward , Tran James , Missling Christopher U. , Ette Ene
Published: December 2023

Pharmacokinetic (PK) data from 28 subjects who received 5‐200‐mg single ascending doses of ANAVEX3‐71, formerly AF710B, were analyzed to characterize the PK of ANAVEX3‐71 and its M8 metabolite. PK data from 12 subjects who received 160 mg ANAVEX3‐71 under fed and fasted conditions were analyzed to characterize the effect of food on the PK of the drug and its M8 metabolite. PK was characterized using the standard 2‐stage approach and the nonlinear mixed‐effects modeling approach. Dose proportionality was determined using the power model. Two‐ and 3‐compartment linear PK models were tested for the characterization of the PK of ANAVEX3‐71 and its M8 metabolite. The PK of ANAVEX3‐71 is linear, dose proportional, and time invariant. The drug is rapidly eliminated with a mean (standard deviation) apparent terminal elimination half‐life of 3.56 (4.09) hours, while the M8 metabolite was eliminated with a mean (standard deviation) apparent terminal elimination half‐life of 6.59 (1.64) hours. The population PK model was used to investigate the effects of covariates on the PK of ANAVEX3‐71 and M8. Age, weight, and creatinine clearance were not explanatory of the variability in apparent clearance and apparent volume of the central compartment of ANAVEX3‐71. Food had no effect on the PK of ANAVEX3‐71 and its M8 metabolite.
Metabolite Bioanalysis in Drug Development: Recommendations from the IQ Consortium Metabolite Bioanalysis Working Group
Authors: Li Wenkui , Vazvaei‐Smith Faye , Dear Gordon , Boer Jason , Cuyckens Filip , Fraier Daniela , Liang Yuexia , Lu Ding , Mangus Heidi , Moliner Patricia , Pedersen Mette Lund , Romeo Andrea A. , Spracklin Douglas K. , Wagner David S. , Winter Serge , Xu Xiaohui (Sophia)
Published: December 2023

The intent of this perspective is to share the recommendations of the International Consortium for Innovation and Quality in Pharmaceutical Development Metabolite Bioanalysis Working Group on the fit‐for‐purpose metabolite bioanalysis in support of drug development and registration. This report summarizes the considerations for the trigger, timing, and rigor of bioanalysis in the various assessments to address unique challenges due to metabolites, with respect to efficacy and safety, which may arise during drug development from investigational new drug (IND) enabling studies, and phase I, phase II, and phase III clinical trials to regulatory submission. The recommended approaches ensure that important drug metabolites are identified in a timely manner and properly characterized for efficient drug development.
Adolescent morphine exposure changes the endogenous vlPAG opioid response to inflammatory pain in rats
Authors: Alami Kawsar , Ghasemi Elmira , Semnanian Saeed , Azizi Hossein
Published: December 2023

Adolescence is one of the most critical periods for brain development, and exposure to morphine during this period can have long‐life effects on pain‐related behaviors. The opioid system in the periaqueductal gray (PAG) is highly vulnerable to drug exposure. However, the impact of adolescent morphine exposure (AME) on the endogenous opioid system in the PAG is currently unknown. This study aims to investigate the long‐lasting effects of AME on the endogenous opioid system and its involvement in altering nociceptive behaviors. Adolescent rats were given escalating doses of morphine (2.5–25 mg/kg, subcutaneous) or an equal volume of saline twice daily for 10 consecutive days (PND 31–40). After a 30‐day washout period, adult rats underwent formalin tests following microinjection of morphine, naloxone, or saline into the ventrolateral PAG (vlPAG) region. The results indicated that morphine microinjection into the vlPAG of the adolescent morphine‐treated group significantly reduced the nociceptive score. However, the analgesic response to morphine in this group was significantly lower compared to the saline‐treated group during adolescence. Additionally, the nociceptive score significantly increased following naloxone but not saline microinjection into the vlPAG of the saline‐treated group during adolescence, rather than the morphine‐treated one. These findings indicate that AME has long‐lasting effects on the endogenous opioid system in the vlPAG, which can consequently alter behaviors related to inflammatory pain in adulthood.
Graphene Nanoribbons Enhancing the Electronic Conductivity and Ionic Diffusion of Graphene Electrodes for High‐Performance Microsupercapacitors
Authors: Zhang Yan , Zhang Huandi , Wang Xiaoxiao , Shi Xiaowei , Zhao Zehua , Wang Yaling , Liu Jiamei , Tang Cheng , Wang Guolong , Li Lei
Published: December 2023

The electrochemical performance of microsupercapacitors with graphene electrodes is reduced by the issue of graphene sheets aggregation, which limits electrolyte ions penetration into electrode. Increasing the space between graphene sheets in electrodes facilitates the electrolyte ions penetration, but sacrifices its electronic conductivity which also influences the charge storage ability. The challenging task is to improve the electrodes' electronic conductivity and ionic diffusion simultaneously, boosting the device's electrochemical performance. Herein, we experimentally realize the enhancement of both electronic conductivity and ionic diffusion from 2D graphene nanoribbons assisted graphene electrode with porous layer‐upon‐layer structure, which is tailored by graphene nanoribbons and self‐sacrificial templates ethyl cellulose. The designed electrode‐based device delivers a high areal capacitance of 71 mF cm−2 and areal energy density of 9.83 μWh cm−2, promising rate performance, outstanding cycling stability with 97% capacitance retention after 20 000 cycles, and good mechanical properties. The strategy paves the way for fabricating high‐performance graphene‐based MSCs.
Toluene Processed All‐Polymer Solar Cells with 18% Efficiency and Enhanced Stability Enabled by Solid Additive: Comparison Between Sequential‐Processing and Blend‐Casting
Authors: Zhang Guoping , Zhao Chaoyue , Zhu Liangxiang , Wang Lihong , Xiong Wenzhao , Hu Huawei , Bai Qing , Wang Yaping , Xie Chen , You Peng , Yan He , Wu Dan , Yang Tao , Qiu Mingxia , Li Shunpu , Zhang Guangye
Published: December 2023

The emergence of polymerized small molecule acceptors (PSMAs) has significantly improved the performance of all‐polymer solar cells (all‐PSCs). However, the pace of device engineering lacks behind that of materials development, so that a majority of the PSMAs have not fulfilled their potentials. Furthermore, most high‐performance all‐PSCs rely on the use of chloroform as the processing solvent. For instance, the recent high‐performance PSMA, named PJ1‐γ, with high LUMO, and HOMO levels, could only achieve a PCE of 16.1% with a high‐energy‐level donor (JD40) using chloroform. Herein, we present a methodology combining sequential processing (SqP) with the addition of 0.5%wt PC71BM as a solid additive (SA) to achieve an impressive efficiency of 18.0% for all‐PSCs processed from toluene, an aromatic hydrocarbon solvent. Compared to the conventional blend‐casting (BC) method whose best efficiency (16.7%) could only be achieved using chloroform, the SqP method significantly boosted the device efficiency using toluene as the processing solvent. In addition, the donor we employ is the classic PM6 that has deeper energy levels than JD40, which provides low energy loss for the device. We compare the results with another PSMA (PYF‐T‐o) with the same method. Finally, an improved photostability of the SqP devices with the incorporation of SA is demonstrated.
In Situ‐Constructed LixMoS2 with Highly Exposed Interface Boosting High‐Loading and Long‐Life Cathode for All‐Solid‐State Li–S Batteries
Authors: Li Hao , Wang Rui , Song Jiangping , Liu Dan , Gao Hongyang , Chao Yimin , Tang Haolin
Published: December 2023

As the persistent concerns regarding sluggish reaction kinetics and insufficient conductivities of sulfur cathodes in all‐solid‐state Li–S batteries (ASSLSBs), numerous carbon additives and solid‐state electrolytes (SSEs) have been incorporated into the cathode to facilitate ion/electron pathways around sulfur. However, this has resulted in a reduced capacity and decomposition of SSEs. Therefore, it is worth exploring neotype sulfur hosts with electronic/ionic conductivity in the cathode. Herein, we present a hybrid cathode composed of few‐layered S/MoS2/C nanosheets (<5 layers) that exhibits high‐loading and long‐life performance without the need of additional carbon additives in advanced ASSLSBs. The multifunctional MoS2/C host exposes the abundant surface for intimate contacting sites, in situ‐formed LixMoS2 during discharging as mixed ion/electron conductive network improves the S/Li2S conversion, and contributes extra capacity for the part of active materials. With a high active material content (S + MoS2/C) of 60 wt% in the S/MoS2/C/Li6PS5Cl cathode composite (the carbon content is only ~3.97 wt%), the S/MoS2/C electrode delivers excellent electrochemical performance, with a high reversible discharge capacity of 980.3 mAh g−1 (588.2 mAh g−1 based on the whole cathode weight) after 100 cycles at 100 mA g−1. The stable cycling performance is observed over 3500 cycles with a Coulombic efficiency of 98.5% at 600 mA g−1, while a high areal capacity of 10.4 mAh cm−2 is achieved with active material loading of 12.8 mg cm−2.
Gravity‐driven flow control in a fully integrated microfluidic cartridge for molecular point‐of‐care testing
Authors: Zai Yunfeng , Wang Zunliang , Ding Yongjun , Min Chao , Liu Yuan , Zhao Huan , Su Enben , He Nongyue
Published: December 2023

Molecular point‐of‐care testing (POCT) system is crucial for the timely prevention and control of infectious diseases. We recently proposed a gravity‐driven microfluidic cartridge for molecular POCT detection, without the need for external sources or actuators, demonstrating the advantages in terms of the reduced cartridge size and low development costs. How to achieve precise control of liquid flow behavior is challenging for the gravity‐driven cartridge. In this work, we explored the underlying mechanism of flow control in the cartridge and offered optimized solutions for our cartridge design to achieve precise control of dynamic flow rates and enhance pumping efficiency significantly. Through the computational fluid dynamics simulations, we demonstrated that adopting an asymptotic contraction chamber geometry design and a closed‐loop air flow channel design with the cartridge inlet can facilitate stable laminar flow of the liquid in our microfluidic cartridge, enabling precise control of flow velocity. We further optimized the microchannel diameter and the contact angle of the liquid with the microchannel wall. The effectiveness of the optimized cartridge for POCT detection was well validated by the accurate detection of the human papillomavirus type 16 virus in the 120 clinical swab samples.
Carbon Pricing is not Unjust
Authors: Mintz‐Woo Kian
Published: December 2023

The aim of this perspective is to argue that carbon pricing is not unjust. Two important dimensions of justice are distributive and procedural (sometimes called “participatory”) justice. In terms of distributive justice, it is argued that carbon pricing can be made distributionally just through revenue recycling and that it should be expected that even neutral reductions in emissions will generate progressive benefits, both internationally and regionally. In terms of procedural justice, it is argued that carbon pricing is in principle compatible with any procedure; however, there is also a particular morally justifiable procedure, the Citizens’ Assembly, which has been implemented in Ireland on this precise question and has generated broad agreement on carbon pricing. It is suggested that this morally matters because such groups are like “ideal advisors” that offer morally important advice. Finally, an independent objection is offered to some ambitious alternatives to carbon pricing like Green New Deal‐type frameworks, frameworks that aim to simultaneously tackle multiple social challenges. The objection is that these will take too long to work in a climate context, both to develop and to iterate.
Towards inclusive transport: The responsiveness of intercity bus services to the needs of people with disabilities in Tamale, Ghana
Authors: Akaateba Millicent Awialie , Adumpo Emile Akangoa , Yakubu Ibrahim
Published: December 2023

People with disabilities (PWDs) have an equal right to independent mobility and dignified involvement in society, which is intrinsically related to their access to inclusive public transit systems. Yet, very often PWDs face injustices of unequal mobilities emanating from a combination of access barriers. Based on qualitative interviews and Focus Group Discussions with PWDs and station managers, this exploratory study assessed the responsiveness of public intercity bus services to the needs of PWDs with vision, hearing and walking/climbing difficulties. The findings show that, despite the Persons with Disabilities Act's passage in 2006, intercity public bus transportation services in Tamale, Ghana, do not meet the needs of PWDs. Intercity bus stations and vehicles are not disability‐friendly, leading to people with disabilities facing severe discrimination and having a more difficult time using intercity bus services. This is due to a combination of environmental barriers, legislative/policy inadequacies, negative public attitudes and low compliance of transport operators to transport provisions in the Disability Act. PWDs express deep‐seated feelings of marginalisation and resentment about the uneven access to transport services and the violation of their rights to autonomy in movement. It is concluded that the journey experiences of PWDs have a significant adverse influence on their travel decisions and full participation in society. Hence, suggestions for further research and policy recommendations to promote inclusive transport systems have been proffered.
BRAF and MEK inhibitor combinations induce potent molecular and immunological effects in NRAS‐mutant melanoma cells: Insights into mode of action and resistance mechanisms
Authors: Dinter Lisa , Karitzky Paula C. , Schulz Alexander , Wurm Alexander A. , Mehnert Marie‐Christin , Sergon Mildred , Tunger Antje , Lesche Mathias , Wehner Rebekka , Müller Anja , Käubler Theresa , Niessner Heike , Dahl Andreas , Beissert Stefan , Schmitz Marc , Meier Friedegund , Seliger Barbara , Westphal Dana
Published: December 2023

About 25% of melanoma harbor activating NRAS mutations, which are associated with aggressive disease therefore requiring a rapid antitumor intervention. However, no efficient targeted therapy options are currently available for patients with NRAS‐mutant melanoma. MEK inhibitors (MEKi) appear to display a moderate antitumor activity and also immunological effects in NRAS‐mutant melanoma, providing an ideal backbone for combination treatments. In our study, the MEKi binimetinib, cobimetinib and trametinib combined with the BRAF inhibitors (BRAFi) encorafenib, vemurafenib and dabrafenib were investigated for their ability to inhibit proliferation, induce apoptosis and alter the expression of immune modulatory molecules in sensitive NRAS‐mutant melanoma cells using two‐ and three‐dimensional cell culture models as well as RNA sequencing analyses. Furthermore, NRAS‐mutant melanoma cells resistant to the three BRAFi/MEKi combinations were established to characterize the mechanisms contributing to their resistance. All BRAFi induced a stress response in the sensitive NRAS‐mutant melanoma cells thereby significantly enhancing the antiproliferative and proapoptotic activity of the MEKi analyzed. Furthermore, BRAFi/MEKi combinations upregulated immune relevant molecules, such as ICOS‐L, components of antigen‐presenting machinery and the “don't eat me signal” molecule CD47 in the melanoma cells. The BRAFi/MEKi‐resistant, NRAS‐mutant melanoma cells counteracted the molecular and immunological effects of BRAFi/MEKi by upregulating downstream mitogen‐activated protein kinase pathway molecules, inhibiting apoptosis and promoting immune escape mechanisms. Together, our study reveals potent molecular and immunological effects of BRAFi/MEKi in sensitive NRAS‐mutant melanoma cells that may be exploited in new combinational treatment strategies for patients with NRAS‐mutant melanoma.
Tongue microarchitecture and functional characterization of the lingual papillae in the desert hedgehog (Paraechinus aethiopicus)
Authors: Massoud Diaa , AbdRabou Mervat A. , Fouda Maged , Shaldoum Fayez , Alrashdi Barakat M. , Germoush Mousa O. , Alfassam Haifa E. , Al‐ Otaibi Aljohara M. , Soliman Soha A. , Abd‐Elhafeez Hanan H. , Hassan Mervat , Mahmoud Ayman M.
Published: December 2023

The present work attempted to provide a comprehensive description of the morphoanatomical, histological, and ultrastructural characteristics of the tongue in the desert hedgehog (Paraechinus aethiopicus), and to correlate lingual modifications to the feeding lifestyle. Five adult male hedgehogs were utilized in our investigation. The macroscopic observations revealed elongated, with a moderately pointed apex, tongue and the tongue dorsum lacks both lingual prominence and median sulcus. The main subdivisions of the tongue are radix linguae (root), corpus linguae (body), and apex linguae (apex). The tongue dorsum carries two types of mechanical (conical and filiform) and gustatory (fungiform and circumvallate) papillae. The lingual apex is characterized by the existence of a unique encapsulated muscular structure. Additionally, the lingual glands were interposed between the muscular strands and no lingual glands were detected on the lingual apex. The dorsal surface of the lingual apex exhibited the highest level of keratinization as revealed by histochemical staining while the root showed moderate staining. The topography of the tongue was investigated by scanning electron microscopy (SEM). The obtained results are important to provide basic knowledge that can contribute to better understanding of the nourishment, feeding habits and behavior in this species. Furthermore, the addition of the newly investigated species may help us to determine the evolutionary relationships among species.
[11C]CO2 BOP fixation with amines to access 11C‐labeled ureas for PET imaging
Authors: Bonnemaire Coralie M. , Windhorst Albert D. , Orru Romano , Ruijter Eelco , Vugts Danielle J.
Published: December 2023

Carbon‐11 (11C) is a widely used radionuclide for positron emission tomography (PET) owing to the omnipresence of carbon atoms in organic molecules. While its half‐life of 20.4 min is ideal for imaging and dosimetry, it also limits the synthetic possibilities. As such, the development of fast and easy, high‐yielding synthesis methods is crucial for the application of 11C‐labeled tracers in humans.

In this study, we present a novel and efficient method for the reaction of [11C]CO2 with amine precursors using benzotriazole‐1‐yl‐oxy‐tris‐(dimethylamino)‐phosphonium hexafluorophosphate (BOP) to access 11C‐labeled ureas. Our method is extremely fast as it only requires transfer of [11C]CO2 into a solution with precursor and BOP at room temperature, where it reacts momentary into the desired 11C‐labeled urea. This simple procedure makes it possible to radiolabel urea directly from [11C]CO2 without the need for advanced equipment, making the method applicable for all laboratories where [11C]CO2 is available. We synthesized a small series of aliphatic symmetrical and non‐symmetrical 11C‐labeled ureas using this method, and achieved good to excellent yields.

The novelty of our study lies in the fact that peptide coupling reagent BOP is used for the first time in radiochemistry to activate [11C]CO2, facilitating its reaction with amines to obtain 11C‐labeled ureas.
Viral AMGs‐driven pentose phosphate pathway in natural wetland
Authors: Li Yanmei , Yu Hang , Xiong Lingling , Wei Yunlin , Li Haiyan , Ji Xiuling
Published: December 2023

Viruses exist anywhere on earth where there is life, and among them, virus‐encoded auxiliary metabolic genes (AMGs) can maintain ecosystem balance and play a major role in the global ecosystem. Although the function of AMGs has been widely reported, the genetic diversity of AMGs in natural ecosystems is still poorly understood. Exploring the genetic diversity of viral community‐wide AMGs is essential to gain insight into the complex interactions between viruses and hosts. In this article, we studied the phylogenetic tree, principal co‐ordinates analysis (PCoA), α diversity, and metabolic pathways of viral auxiliary metabolism genes involved in the pentose phosphate pathway (PPP) through metagenomics, and the changes of metabolites and genes of host bacteria were further studied by using Pseudomonas mandelii SW‐3 and its lytic phage based on metabolic flow and AMGs expression. We found that the viral AMGs in the Napahai plateau wetland were created by a combination of various external forces, which contributed to the rich genetic diversity, uniqueness, and differences of the virus, which promoted the reproduction of offspring and better adaptation to the environment. Overall, this study systematically describes the genetic diversity of AMGs associated with the PPP in plateau wetland ecosystems and further expands the understanding of phage–host unique interactions.
The recent evolution of the salt marsh ‘Pantano Grande’ (NE Sicily, Italy): interplay between natural and human activity over the last 3700 years
Authors: Palli Jordan , Monaco Lorenzo , Bini Monica , Cosma Emanuela , Giaccio Biagio , Izdebski Adam , Masi Alessia , Mensing Scott , Piovesan Gianluca , Rossi Veronica , Sadori Laura , Wagner Bernd , Zanchetta Giovanni
Published: December 2023

Combined natural processes and human activities shaped the late Holocene landscape history in many Mediterranean regions. This is especially true with areas subjected to specific human interest, such as coastal areas morphologically suitable to the establishment of harbours. Here, we test the hypothesis on the location of the Roman harbour Portus Trajectus in Peloro Cape (NE Sicily, Italy) and describe the evolution of the area over the last 3700 years through lithostratigraphic, geochemical, meiofauna and microfossil analyses performed on a new sediment core recovered from the coastal salt marsh Pantano Grande (aka Lago di Ganzirri). The age–depth model was developed on radiocarbon dates and geochemical fingerprinting of two tephra layers. Results indicate that the area underwent dramatic changes ca. 650 bce. The anthropogenic impact of Greek colonies may have contributed to modifying the coastal environment of Peloro Cape due to their widespread impact on natural resources. This happened at many localities in the Mediterranean, indicating the magnitude of impact of the Greek colonies over the landscape. According to our results, it is unlikely that the current Pantano Grande basin was used as a harbour in Roman times, although the presence of a harbour in the nearby Pantano Piccolo marsh cannot be excluded. Pantano Grande had been isolated from the sea for more than 2000 years. Human intervention in the 19th century halted that isolation and provided the background for the ecological, economic and social functions the salt marsh performs today.
Minimally invasive interval cytoreductive surgery for advanced ovarian cancer
Authors: Melamed Alexander , Eisenhauer Eric L.
Published: December 2023

With the increasing use of neoadjuvant chemotherapy, it has also become apparent that some patients will require a less extensive interval cytoreductive surgery which could be performed as a minimally invasive procedure. This observation, and expertise with minimally invasive surgery for other indications in gynecologic oncology, has driven surgeons in the United States and other countries to perform an increasing portion of interval cytoreductive surgery using minimally invasive techniques. Further observational and trial data will continue to inform which patients are best suited for this approach.
The impact of sex on treatment and outcome in relation to histological subtype in patients with resectable gastric cancer: Results from the randomized CRITICS trial
Authors: Caspers Irene A. , Slagter Astrid E. , Lind Pehr , Sikorska Karolina , Wiklund Katja , Pontén Fredrik , Nordsmark Marianne , van de Velde Cornelis J. H. , Kranenbarg Elma Meershoek‐Klein , van Sandick Johanna W. , Jansen Edwin P. M. , van Laarhoven Hanneke W. M. , Verheij Marcel , van Grieken Nicole C. T. , Cats Annemieke
Published: December 2023

Background and Objective

This study aims to investigate the impact of sex on outcome measures stratified by histological subtype in patients with resectable gastric cancer (GC).

Methods

A post‐hoc analysis of the CRITICS‐trial, in which patients with resectable GC were treated with perioperative therapy, was performed. Histopathological characteristics and survival were evaluated for males and females stratified for histological subtype (intestinal/diffuse). Additionally, therapy‐related toxicity and compliance were compared.

Results

Data from 781 patients (523 males) were available for analyses. Female sex was associated with a distal tumor localization in intestinal (p = 0.014) and diffuse tumors (p < 0.001), and younger age in diffuse GC (p = 0.035). In diffuse GC, tumor‐positive resection margins were also more common in females than males (21% vs. 10%; p = 0.020), specifically at the duodenal margin. During preoperative chemotherapy, severe toxicity occurred in 327 (63%) males and 184 (71%) females (p = 0.015). Notwithstanding this, relative dose intensities were not significantly different between sexes.

Conclusions

Positive distal margin rates were higher in females with diffuse GC, predominantly at the duodenal site. Females also experience more toxicity, but this neither impacts dose intensities nor surgical resection rates. Clinicians should be aware of these different surgical outcomes when treating males and females with GC.
Seasonal and spatial variability of CO2 emissions in a large tropical mangrove‐dominated delta
Authors: Chielle Raisa S.A. , Marins Rozane V. , Cavalcante Mariany S. , Cotovicz Luiz C.
Published: December 2023

This study quantified the seasonal and spatial variability of partial pressure of CO2 (pCO2) and water‐atmosphere CO2 fluxes in the Parnaíba River Delta, the largest delta in the Americas. It is a pristine equatorial, mangrove‐dominated environment located in a transitional between humid and semi‐arid climates, with marked seasonality in rainfall and river discharge. Major channels and bays were sampled during dry and wet seasons, with continuous measurements of pCO2, temperature, salinity, and wind velocity. Subsurface water samples were collected in discrete stations for pH, total alkalinity (TA), dissolved inorganic carbon (DIC), dissolved oxygen and chlorophyll a quantification. A significant positive correlation between carbonate system parameters with salinity was found in both periods, with salinity significantly higher in the dry season. Strong deviations of pCO2, TA, and DIC from two endmembers conservative mixing were found, particularly in mangrove‐dominated waters, due to organic matter degradation. The Delta showed high spatial variability of pCO2, with the highest values in mangrove‐dominated waters, moderate in the river‐dominated regions, and lowest in the high salinity areas, suggesting that pCO2 variability is likely controlled by a combination of river‐ocean mixing and biological processes (respiration and photosynthesis). The Delta outgasses about 20 times less CO2 in the dry season (9.06 ± 11.09 mmol m−2.d−1) than in the rainy season (209.68 ± 250.87 mmol m−2 d−1). Our results indicate this large mangrove‐dominated tropical delta is an important source of CO2 to the atmosphere, but a sharp decrease was observed during dry periods.
Oral Troxerutin Alleviates Depression Symptoms in Mice by Modulating Gut Microbiota and Microbial Metabolism
Authors: Lan Zhi‐fang , Yao Wei , Xie Yi‐ci , Chen Wushisi , Zhu Yin‐ying , Chen Jia‐qi , Zhou Xing‐yi , Huang Jun‐qing , Wu Man‐si , Chen Jia‐xu
Published: December 2023

Scope

A growing body of evidence suggests that the harmful gut microbiota in depression patients can play a role in the progression of depression. There is limited research on troxerutin's impact on the central nervous system (CNS), especially in depression. The study finds that troxerutin effectively alleviates depression and anxiety‐like behavior in mice by increasing the abundance of beneficial bacteria like Lactobacillus and Firmicutes while decreasing the abundance of harmful bacteria like Proteobacteria, Bacteroides, and Actinobacteria in the gut. Furthermore, the research reveals that troxerutin regulates various metabolic pathways in mice, including nucleotide metabolism, caffeine metabolism, purine metabolism, arginine biosynthesis, histidine metabolism, 2‐oxocarboxylic acid metabolism, biosynthesis of amino acids, glycine, serine and threonine metabolism, and Arginine and proline metabolism.

Conclusions

In conclusion, the study provides compelling evidence for the antidepressant efficacy of troxerutin. Through the investigation of the role of intestinal microorganisms and metabolites, the study identifies these factors as key players in troxerutin's ability to prevent depression. Troxerutin achieves its neuroprotective effects and effectively prevents depression and anxiety by modulating the abundance of gut microbiota, including Proteobacteria, Bacteroides, and Actinobacteria, as well as regulating metabolites such as creatine.
Microstrip‐line‐based K‐band isolator and Ku‐band phase shifter with barium hexa ferrite disc
Authors: Akkapanthula Sai Haranadh , Kagita Srujana , Voma U. K.
Published: December 2023

This article deals with the operational behavior of barium hexaferrite (BHF) disc when incorporated in microwave substrates for wireless applications. A microstrip line printed on a Rogers substrate (35 mm × 35 mm × 1.6 mm) has been used in the design to observe the effect of BHF material. A BHF circular‐shaped disc of radius 4.5 mm and thickness 1 mm is inserted in the middle of the microstrip line. The ferrite is biased using miniature lightweight neodymium magnets stacked one over the other to obtain desired magnetic field strength. The proposed microstrip line inserted with a BHF disc exhibits wide band isolation properties in the K‐band (15–21 GHz) with an average isolation of 20 dB and peak isolation of 51 dB centered at 18.5 GHz. It is observed that the same circuit is behaving as a phase shifter showing a 45° ± 3° phase shift in the band ranging from 12 to 14 GHz. The proposed compact microstrip‐line circuit can be used as both ferrite phase shifter and isolator in consecutive bands (Ku‐ and K‐bands) with ease of integration and biasing.
Treatment practices and response in kaposiform hemangioendothelioma: A multicenter cohort study
Authors: Borst Alexandra J. , Eng Whitney , Griffin Morgan , Ricci Kiersten W. , Engel Elissa , Adams Denise M. , Dayneka Jillian , Cohen‐Cutler Sally J. , Andreoli Steven M. , Wu Melinda D. , Wheeler Allison P. , Heym Kenneth M. , Crary Shelley E. , Nakano Taizo A. , Schulte Rachael R. , Setty Bhuvana A. , McLean Thomas W. , Pahl Kristy S. , Intzes Stefanos , Pateva Irina , Teitelbaum Max , Zong Zili , Li Yimei , Jeng Michael R.
Published: December 2023

Background and objectives

Kaposiform hemangioendothelioma (KHE) and tufted angioma (TA) are rare vascular tumors in children historically associated with significant morbidity and mortality. This study was conducted to determine first‐line therapy in the absence of available prospective clinical trials.

Methods

Patients from 17 institutions diagnosed with KHE/TA between 2005 and 2020 with more than 6 months of follow‐up were included. Response rates to sirolimus and vincristine were compared at 3 and 6 months. Durability of response and response to other treatment modalities were also evaluated.

Results

Of 159 unique KHE/TA subjects, Kasabach–Merritt phenomenon (KMP) was present in 64 (40.3%), and only two patients were deceased (1.3%). Over 60% (n = 96) demonstrated treatment response at 3 months, and more than 70% (n = 114) by 6 months (no significant difference across groups). The vincristine group had higher radiologic response at 3 months compared to sirolimus (72.7% vs. 20%, p = .03), but there were no differences between these groups at 6 months. There were no differences in rates of recurrent or progressive disease between vincristine and sirolimus.

Conclusions

In this large, multicenter cohort of 159 patients with KHE/TA, rates of KMP were consistent with historical literature, but the mortality rate (1.3%) was much lower. Overall treatment response rates were high (>70%), and there was no significant difference in treatment response or durability of disease comparing sirolimus to vincristine. Our results support individualized treatment decision plans depending on clinical scenario and patient/physician preferences. Response criteria and response rates reported here will be useful for guiding future treatment protocols for vascular tumors.
Hemostatic balance between pro‐ and anticoagulant is maintained during glucocorticoid treatment
Authors: Yamashita Atsuki , Nagae Chiai , Umezawa Yotaro , Mori Mika , Ashikaga Tomoko , Akita Mieko , Suzuki Noriko , Yamazaki Satoshi , Takayama Shigenobu , Taki Masashi
Published: December 2023

Background

Glucocorticoids are associated with an increased risk of venous thrombosis. Glucocorticoid treatment increases coagulation factor and anticoagulant levels; however, its effect on hemostatic function remains unclear. This study aimed to investigate the changes in comprehensive coagulation profiles after glucocorticoid treatment in noninflammatory diseases to elucidate the direct contribution of glucocorticoids to hemostatic function.

Procedure

Patients diagnosed with primary immune thrombocytopenia requiring glucocorticoid treatment were prospectively enrolled in this study. Changes in coagulation factors and anticoagulants during glucocorticoid treatment and changes in thrombin generation potential were determined in the absence and presence of soluble thrombomodulin (sTM).

Results

Seven treatment cases (four for steroid pulse therapy and three for oral glucocorticoid therapy) in six patients with immune thrombocytopenia were examined. After glucocorticoid treatment, activated partial thromboplastin time significantly shortened, and activities of factor VIII, IX, XI, and XII significantly increased, except for von Willebrand factor antigen. Moreover, antithrombin and protein C (PC) activities significantly increased after glucocorticoid treatment. Two major parameters of thrombin generation potential, endogenous thrombin potential (ETP) and peak thrombin (Peak), significantly increased in the absence of sTM after glucocorticoid treatment. However, no significant increases in either parameter were observed in the presence of sTM. ETP‐TM and Peak‐TM ratios, which represent resistance to the anticoagulant effect of the PC pathway, significantly decreased after glucocorticoid treatment, suggesting that anticoagulant function via the PC pathway is elevated after glucocorticoid treatment.

Conclusions

As glucocorticoids increase intrinsic coagulation factor and anticoagulant levels, hemostatic balance between pro‐ and anticoagulant functions is maintained.
Interpersonal psychotherapy for comorbid prolonged grief disorder and persistent depressive disorder in a Japanese patient: A case report
Authors: Okami Takuya , Toshishige Yuko , Kondo Masaki , Okazaki Junya , Mizushima Hiroko , Akechi Tatsuo
Published: December 2023

Background

Prolonged grief disorder (PGD) is a new diagnostic entity. However, treatment for PGD is not yet available. Interpersonal psychotherapy (IPT) may be effective for PGD.

Case Presentation

A single 27‐year‐old Japanese woman lost her brother to suicide. However, she did not express her grief to anyone or visit a psychiatric clinic. After experiencing strong depressive symptoms triggered by work stress, she visited a psychiatric clinic, where she was diagnosed with depression as well as PGD. Through pharmacotherapy, her depressive symptoms improved, but no improvement was noted in her PGD symptoms. She therefore began IPT for PGD at our hospital, 5 years after her brother's suicide and after 4 years of PGD symptoms. In the introductory phase of IPT, she was diagnosed with comorbid persistent depressive disorder (PDD). After this diagnosis, through psychoeducation on PDD, she could identify the symptoms that reflected her personality traits as “PDD symptoms.” Furthermore, she could affirm her positive and negative feelings and share them with others. Consequently, the grieving process was facilitated, and her interests and relationships were re‐established. Her PGD and PDD symptoms improved.

Conclusion

IPT may be effective for PGD comorbid with PDD among Japanese.
Activation of dihydrogen by group‐14 substituted germylenes
Authors: Rahmati Somayeh , Ayoubi‐Chianeh Mojgan , Kassaee Mohamad Z.
Published: December 2023

We have investigated the structural and thermodynamic parameters of group‐14 substituted germylenes and their reactivity toward the H2 molecule using density functional theory (DFT). We conducted the detailed Kohn–Sham molecular orbital (KS‐MO) analysis to quantify the effective factors behind the increased reactivity of germylenes in going from C to Sn as substituents. The quantum theory of atoms in molecules (QTAIM), non‐covalent interaction (NCI), and natural bond orbital (NBO) analyses revealed the nature of bonds and interactions and demonstrated the reactivity trend of germylenes in the presence of H2. The results showed that in going from C to Sn, the reactivity increased due to an improvement in
‐donation interaction between the filled lone‐pair orbital of the germylene (LPGe) and the
*‐orbital of H2, which decreased the reaction barrier (
E‡). As the germylene substitution was varied from C to Sn, a significant reactivity was observed for the germylene toward the H2. This observation was caused by a reduction in steric repulsion between the germylene and the H2 and less activation energy due to the higher
‐donation and lower back‐donation. We have presented the reactivity of new and rationally designed germylenes toward H2 using various analyses that will serve as a guide for the activation of small molecules such as H2, which is employed in many subsequent reactions.
Recent developments in fluorine‐containing pesticides
Authors: Jeschke Peter
Published: December 2023

To ensure ongoing sustainability, the modern agrochemical industry is faced with enormous challenges. These arise from provision of high‐quality food to increasing water use and environmental impact as well as a growing world population. The loss of previous agrochemicals due to consumer perception, changing grower needs and ever‐changing regulatory requirements is higher than the number of active ingredients that are being introduced into the crop protection market. Therefore, the development of novel agrochemicals is essential to provide improved efficacy and environmental profiles. In this context, the introduction of fluorine atoms and fluorine‐containing motifs into a molecule is an important method to influence its physicochemical properties. These include, for example, small difluoro‐ and trifluoromethyl, or trifluoromethoxy groups at aryl or heterocyclic aryl moieties but also fragments like 2,2,2‐trifluoroethoxycarbonyl, trifluoromethylsulfonyl, trifluoroacetyl, as well as the so far unusal rest like heptafluoro‐iso‐propyl. This review gives an overview of recent developments of fluorine‐containing pesticides launched over the past 7 years and describes a selection of current fluorine‐containing development candidates. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
A two‐step machine‐learning approach to statistical post‐processing of weather forecasts for power generation
Authors: Baran Ágnes , Baran Sándor
Published: December 2023

By the end of 2021, the renewable energy share of the global electricity capacity reached 38.3% and the new installations were dominated by wind and solar energy, showing global increases of 12.7% and 18.5% respectively. However, both wind and photovoltaic energy sources are highly volatile, making planning difficult for grid operators; thuss, accurate forecasts of the corresponding weather variables are essential for reliable electricity predictions. The most advanced approach in weather prediction is the ensemble method, which opens the door for probabilistic forecasting. However, ensemble forecasts are often underdispersive and subject to systematic bias. Hence, they require some form of statistical post‐processing, where parametric models provide full predictive distributions of the weather variables at hand. We propose a general two‐step machine‐learning‐based approach to calibrating ensemble weather forecasts, where, in the first step, improved point forecasts are generated, which then together with various ensemble statistics serve as input features of the neural network estimating the parameters of the predictive distribution. In two case studies based on 100 m wind speed and global horizontal irradiance forecasts of the operational ensemble prediction system of the Hungarian Meteorological Service, the predictive performance of this novel method is compared with the forecast skill of the raw ensemble and the state‐of‐the‐art parametric approaches. Both case studies confirm that, at least up to 48 hr, statistical post‐processing substantially improves the predictive performance of the raw ensemble for all forecast horizons considered. The variants of the proposed two‐step method investigated outperform in skill their competitors, and the suggested new approach is well applicable for different weather quantities and for a fair range of predictive distributions.