bluuebunny/crossref_metadata_2025 huggingface dataset:
PLD‐Grown Semi‐Insulating Ga2O3 Thin Film‐Based Optoelectronic Artificial Synaptic Devices for Neuromorphic Computing Applications
Authors: Kaur Amandeep , Sikdar Subhrajit , Yadav Santosh Kumar , Dhar Subhabrata
Published: July 2024

Development of artificial opto‐electronic synaptic devices plays a crucial role for the practical implementation of energy‐efficient, parallel processing of human brain. In this article, two terminal inter‐digitated devices are fabricated on Gallium oxide (Ga2O3) thin films grown on sapphire substrates by pulsed laser deposition (PLD) technique to study its ability to mimic biological synaptic behaviors. The layers are found to exhibit long persistent photo‐conductivity (PPC) effect, which is identified to be the key parameter to replicate the behavior of biological synapses. Channel resistance and PPC time constants should also be optimized to improve the efficiency of response and energy consumption of synaptic devices. It has been observed that both conductivity and the PPC decay time of Ga2O3‐films can be controlled by varying oxygen pressure and growth temperature (TG). These devices demonstrate their ability to perform paired pulse facilitation (PPF) at very low applied bias in mV‐range. They can mimic biological synapses showing short‐to‐long‐term memory transition (STM‐to‐LTM) and learning‐forgetting behavior. One of these devices is found to show synaptic behavior with the energy consumption of as low as 71fJ electrical and 21nJ optical per synaptic event. These findings thus strengthen the candidature of Ga2O3 films for the development of next‐generation opto‐electronic neuromorphic devices and systems.
Accessing 2‐(Chalcogen)benzothiazoles via Electrochemical Intermolecular Cyclization of Isocyanides with Thiols or Diselenides
Authors: Zhang Yi , Mo Zu‐Yu , Tang Xin‐Yu , Tang Hai‐Tao , Pan Ying‐Ming , Yang Ke‐Di , Huang Yong‐Lin , He Mu‐Xue
Published: July 2024

2‐(chalcogen)benzothiazoles are frequently used as core structures for the development of pharmaceutical agents. A strategy for the synthesis of 2‐(chalcogen)benzothiazoles under electrooxidative conditions using isocyanides, thiols or diselenides as substrates was developed. This protocol allows access to structurally diverse 2‐(chalcogen)benzothiazoles in good yields and with good functional group tolerance, which does not require heavy metal catalysts and exogenous oxidants. Furthermore, gram‐scale synthesis was performed to demonstrate the scale‐up applicability of this reaction.
EBV‐positive diffuse large B‐cell lymphoma, not otherwise specified: 2024 update on the diagnosis, risk‐stratification, and management
Authors: Malpica Luis , Marques‐Piubelli Mario L. , Beltran Brady E. , Chavez Julio C. , Miranda Roberto N. , Castillo Jorge J.
Published: July 2024

Disease overview

Epstein Barr virus‐positive (EBV+) diffuse large B‐cell lymphoma (DLBCL), not otherwise specified (NOS) is an aggressive B‐cell lymphoma associated with EBV infection included in the WHO classification of lymphoid neoplasms since 2016. Although historically associated to poor prognosis, outcomes seem to have improved in the era of chemoimmunotherapy.

Diagnosis

The diagnosis is established through meticulous pathological evaluation. Detection of EBV‐encoded RNA (EBER) is the standard diagnostic method. The ICC 2022 specifies EBV+ DLBCL, NOS as occurring when >80% of malignant cells express EBER, whereas the WHO‐HAEM5 emphasizes that the majority of tumor cells should be EBER positive without setting a defined threshold. The differential diagnosis includes plasmablastic lymphoma, DLBCL associated with chronic inflammation, primary effusion lymphoma, among others.

Risk‐stratification

The International Prognostic Index (IPI) and the Oyama score can be used for risk‐stratification. The Oyama score includes age >70 years and presence of B symptoms. The expression of CD30 and PD‐1/PD‐L1 are emerging as potential adverse but targetable biomarkers.

Management

Patients with EBV+ DLBCL, NOS, should be staged and managed following similar guidelines than patients with EBV‐negative DLBCL. EBV+ DLBCL, NOS, however, might have a worse prognosis than EBV‐negative DLBCL in the era of chemoimmunotherapy. Therefore, inclusion of patients in clinical trials when available is recommended. There is an opportunity to study and develop targeted therapy in the management of patients with EBV+ DLBCL, NOS.
Organ weights and length anthropometry measures at autopsy for sudden infant death syndrome cases and other infant deaths in the Chicago infant mortality study
Authors: Mychaleckyj Josyf C. , Normeshie Cornelius , Keene Keith L. , Hauck Fern R.
Published: July 2024

Organ weights are a possible diagnostic or pathophysiological clue to distinguishing sudden infant death syndrome (SIDS) cases from other infant deaths but suffer from major confounding. Using autopsy data from the Chicago Infant Mortality Study, a majority African‐American case–control study of deceased infants under 1 year conducted 1993–96, we assessed differences in the weights of brain, thymus, kidneys, lungs, liver, spleen, total body, and four length anthropometry measures in SIDS‐diagnosed infants compared to controls. Using exact and coarsened matching, we ran Bayesian linear models with these anthropometry outcomes and repeated the analyses substituting the corresponding fitted allometrically‐scaled organ weight indices to account for body size. After detailed analysis and adjustment for potential confounders, we found that matched SIDS infants were generally bigger than controls, with higher mean brain, liver, spleen, thymus, lung, and total body weights, and higher mean head and chest circumference, crown‐heel, crown‐rump lengths. SIDS infants also had higher mean thymus, liver, spleen, lung and total body weight indices. The association with thymus weight was proportionately greater in magnitude than any other outcome measure and independent of body size. The results of these more detailed analyses are consistent with recent findings from other studies with differing racial compositions, and substantially confirm the primary organ sites for more detailed mechanistic research into the biological dysregulation contributing to underlying pathophysiology of SIDS.
Impact of elexacaftor/tezacaftor/ivacaftor CFTR modulator therapy on rates of endoscopic sinus surgery in cystic fibrosis
Authors: Pingree Graham , Bentan Mihai , Fitzpatrick Thomas , Schuman Theodore
Published: July 2024

Background

Elexacaftor/tezacaftor/ivacaftor (ETI), a combination cystic fibrosis transmembrane receptor (CFTR) modulator, has demonstrated improved pulmonary outcomes in individuals with cystic fibrosis (CF). However, ETI's impact on functional endoscopic sinus surgery (FESS) remains unclear.

Methods

The TriNetX Analytics Research Network, consisting of 120 million global de‐identified electronic medical records, was queried from 2012 to 2023 for subjects with CF who underwent sinus surgery.1 Patients on ETI prior to FESS (n = 6,056) were propensity score matched to control individuals with CF not on CFTR modulators (n = 37,906) and those on other FDA‐approved CFTR modulators (tezacaftor/ivacaftor, lumacaftor/ivacaftor, and ivacaftor) (n = 2437) based on relevant factors. The primary outcome was the absolute risk reduction (ARR) of undergoing FESS. Secondary outcomes included ARR of CF‐related pulmonary exacerbations and hospital admission from 0 to 6, 6 to 12, and 12 to 24 months following FESS.

Results

ETI use demonstrated a significant ARR for FESS when compared to CF patients not on CFTR modulators (2.12%; 95% confidence interval [CI] 1.5–2.75; p‐value < 0.0001) and those on other CFTR modulators (4.7%; 95% CI 3.54–5.85; p‐value < 0.0001). No significant differences occurred in secondary outcomes between ETI and non‐CFTR modulator groups, except for reduced CF‐related pulmonary exacerbations from 0 to 6 months post‐FESS. Additionally, a significant reduction in pulmonary exacerbations was observed at all time points and hospital admissions within 6 months following FESS compared to those using other CFTR modulators.

Conclusions

In a large dataset, CF patients on ETI demonstrated significantly reduced risk of FESS, pulmonary exacerbations, and hospital admission compared to patients not on CFTR modulators or those on other CFTR modulators, suggesting improved sinonasal disease and overall health status in CF.
The role of revision sinus surgery in the initiation of dupilumab therapy: A real‐world study of molecular and cellular features
Authors: Gaffar Abigail , Alenezi Abdul Rahman , Kelly Kathleen M. , Kulaga Heather M. , Keng Hsin‐Tzu , Smith Amy , Lane Andrew P.
Published: July 2024

Key points

A persistent type 2 endotype signature exists in recalcitrant chronic rhinosinusitis with nasal polyps mucosa on dupilumab.

Revision sinus surgery immediately prior to dupilumab reduces long‐term interleukin (IL)‐4/IL‐13 tissue mRNA.

Pre‐dupilumab revision surgery is associated with reduced tissue eosinophils and GATA‐3+ cells.
Nanoscale flow cytometry‐based quantification of blood‐based extracellular vesicle biomarkers distinguishes MCI and Alzheimer's disease
Authors: Dayarathna Thamara , Roseborough Austyn D. , Gomes Janice , Khazaee Reza , Silveira Carolina R. A. , Borron Kathy , Yu Soojung , Coleman Kristy , Jesso Sarah , Finger Elizabeth , MacDonald Penny , Borrie Michael , Wells Jennie , Bartha Robert , Zou Guangyong , Whitehead Shawn N. , Leong Hon S. , Pasternak Stephen H.
Published: July 2024

INTRODUCTION

Accurate testing for Alzheimer's disease (AD) represents a crucial step for therapeutic advancement. Currently, tests are expensive and require invasive sampling or radiation exposure.

METHODS

We developed a nanoscale flow cytometry (nFC)‐based assay of extracellular vesicles (EVs) to screen biomarkers in plasma from mild cognitive impairment (MCI), AD, or controls.

RESULTS

Circulating amyloid beta (Aβ), tau, phosphorylated tau (p‐tau)181, p‐tau231, p‐tau217, p‐tauS235, ubiquitin, and lysosomal‐associated membrane protein 1–positive EVs distinguished AD samples. p‐tau181, p‐tau217, p‐tauS235, and ubiquitin‐positive EVs distinguished MCI samples. The most sensitive marker for AD distinction was p‐tau231, with an area under the receiver operating characteristic curve (AUC) of 0.96 (sensitivity 0.95/specificity 1.0) improving to an AUC of 0.989 when combined with p‐tauS235.

DISCUSSION

This nFC‐based assay accurately distinguishes MCI and AD plasma without EV isolation, offering a rapid approach requiring minute sample volumes. Incorporating nFC‐based measurements in larger populations and comparison to “gold standard” biomarkers is an exciting next step for developing AD diagnostic tools.

HIGHLIGHTS

Extracellular vesicles represent promising biomarkers of Alzheimer's disease (AD) that can be measured in the peripheral circulation.

This study demonstrates the utility of nanoscale flow cytometry for the measurement of circulating extracellular vesicles (EVs) in AD blood samples.

Multiple markers including amyloid beta, tau, phosphorylated tau (p‐tau)181, p‐tau231, p‐tau217, and p‐tauS235 accurately distinguished AD samples from healthy controls.

Future studies should expand blood and cerebrospinal fluid–based EV biomarker development using nanoflow cytometry approaches.
Pharmacological effects of bioactive agents in earthworm extract: A comprehensive review
Authors: Zhu Zihan , Deng Xinyi , Xie Wenqing , Li Hengzhen , Li Yusheng , Deng Zhenhan
Published: July 2024

This review compiles information from the literature on the chemical composition, pharmacological effects, and molecular mechanisms of earthworm extract (EE) and suggests possibilities for clinical translation of EE. We also consider future trends and concerns in this domain. We summarize the bioactive components of EE, including G‐90, lysenin, lumbrokinase, antimicrobial peptides, earthworm serine protease (ESP), and polyphenols, and detail the antitumor, antithrombotic, antiviral, antibacterial, anti‐inflammatory, analgesic, antioxidant, wound‐healing, antifibrotic, and hypoglycemic activities and mechanisms of action of EE based on existing in vitro and in vivo studies. We further propose the potential of EE for clinical translation in anticancer and lipid‐modifying therapies, and its promise as source of a novel agent for wound healing and resistance to antibiotic tolerance. The earthworm enzyme lumbrokinase embodies highly effective anticoagulant and thrombolytic properties and has the advantage of not causing bleeding phenomena due to hyperfibrinolysis. Its antifibrotic properties can reduce the excessive accumulation of extracellular matrix. The glycolipoprotein extract G‐90 can effectively scavenge reactive oxygen groups and protect cellular tissues from oxidative damage. Earthworms have evolved a well‐developed defense mechanism to fight against microbial infections, and the bioactive agents in EE have shown good antibacterial, fungal, and viral properties in in vitro and in vivo experiments and can alleviate inflammatory responses caused by infections, effectively reducing pain. Recent studies have also highlighted the role of EE in lowering blood glucose. EE shows high medicinal value and is expected to be a source of many bioactive compounds.
Pfadunabhängiges mit sichtbarem Licht adressierbares orthogonales Photoschalten für Anwendungen in multi‐photochromomen Polymeren und molekularen Computern
Authors: Köttner Laura , Dube Henry
Published: July 2024

Synthetische molekulare Photoschalter sind als hochpräzise Werkzeuge zur Einführung von Lichtadressierbarkeit auf kleinster Ebene in den Mittelpunkt der Forschung gerückt. Heute sind sie in allen Bereichen der angewandten Chemie zu finden, sei es in der Materialforschung, chemischen Biologie, Katalyse oder Nanotechnologie. Für einen nächsten Schritt in der Anwendbarkeit ist vollständig orthogonales Photoschalten besonders wünschenswert, aber bis heute ist eine solche unabhängige Adressierbarkeit verschiedener Photoschalter eine große Herausforderung. In dieser Arbeit präsentieren wir das erste Beispiel für ein vollständig durch sichtbares Licht adressierbares und pfadunabhängiges orthogonales Photoschalten. Durch die Kombination von zwei kürzlich entwickelten indigoiden Photoschaltern – ein peri‐Anthracenthioindigo und ein auf Rhodanin‐basiertes Chromophor – wird ein Schaltsystem mit vier Zuständen geschaffen, wobei jeder Zustand in hoher Ausbeute völlig unabhängig und ausnahmslos mit sichtbarem Licht angesteuert werden kann. Die vier Zustände führen zu vier verschiedenen Farben, die auf eine feste Polymermatrix übertragen werden können, wodurch ein vielseitiges photochromes Material mit multiplen Zuständen entsteht. Darüber hinaus wird die Kombination mit einem Fluoreszenzfarbstoff als dritter Komponente gezeigt, was die Anwendbarkeit dieses orthogonalen Photoschaltersystems in der molekularen Logik und Informationsverarbeitung ermöglicht.
Asymmetric Paired Electrolysis: Enantioselective Alkylation of Sulfonylimines via C(sp3)−H Functionalization
Authors: Tao Yongsheng , Ma Wan , Sun Rui , Huang Cheng , Lu Qingquan
Published: July 2024

Enantioselective transformation of ubiquitous C(sp3)−H bonds into three‐dimensional chiral scaffolds is of longstanding interest to synthetic chemists. Herein, an asymmetric paired electrolysis enables a highly efficient and sustainable approach to the enantioselective alkylation of sulfonylimines via C(sp3)−H functionalization. In this protocol, anodic oxidation for benzylic radical formation and Lewis acid‐catalyzed sulfonylimine reduction on the cathode were seamlessly cross‐coupled (up to 88 % yield). Enantioenriched chiral amines containing a tetrasubstituted carbon stereocenter are accessed with high enantioselectivity (up to 96 % ee). Mechanistic studies suggest that the amine generated in situ could serve as a base to deprotonate phenols and decrease the oxidation potential of the reaction, allowing phenols with lower potentials to be preferentially oxidized.
A Modified Arbuzov‐Michalis Reaction for Selective Alkylation of Nucleophiles
Authors: Wang Jia‐Xi , Chen Mu‐Qiu , Zhang Yang , Han Bo , Mou Ze‐Dong , Feng Xitong , Zhang Xia , Niu Dawen
Published: July 2024

The alkylation of nucleophiles is among the most fundamental and well‐developed transformations in chemistry. However, to achieve selective alkylation of complex substrates remains a nontrivial task. We report herein a general and selective alkylation method without using strong acids, bases, or metals. In this method, the readily available phosphinites/phosphites, in combination with ethyl acrylate, function as effective alkylating agents. Various nucleophilic groups, including alcohols, phenols, carboxylic acids, imides, and thiols can be alkylated. This method can be applied in the late‐stage alkylation of natural products and pharmaceutical agents, achieving chemo‐ and site‐selective modification of complex substrates. Experimental studies indicate the relative reactivity of a nucleophile depends on its acidity and its steric environment. Mechanistic studies suggest the reaction pathway resembles that of the Arbuzov‐Michalis reaction.
A polyurethane elastomer combining high strength and excellent self‐healing properties for waterproofing coatings
Authors: Liu Zhen , Xu Heng , Fan Zhijie , Zhang Xiandie , Cui Xuxu , Ji Jie , Li Haozhe , Guo Xiaode
Published: July 2024

Self‐healing materials have not been able to solve the problem of the coexistence of mechanical strength and self‐healing function. Despite years of research, high‐strength self‐healing materials still require external factors to accelerate their self‐healing process. For this reason, in this study, two kinds of chain extenders were inserted into the hard segment to design the molecular structure of polyurethane. The introduction of two chain extenders not only provided multiple binding modes for hydrogen bond recombination, but also formed more types of hydrogen bonds. Based on the design, a polyurethane elastomer PUGI‐D3B2 with high strength and excellent self‐healing properties was synthesized. Data such as FTIR and 1H NMR spectra clearly demonstrate the successful synthesis of PUGI‐D3B2. The mechanical strength of PUGI‐D3B2 is 15.34 MPa, and its surface scratches can completely disappear after self‐healing at 60°C for 10 h，and 98.02% of the mechanical strength is restored after 12 h of heal. Therefore, combining the excellent self‐healing properties of PUGI‐D3B2, we prepared a multifunctional superhydrophobic material (SHN‐SiO2/PUGI‐D3B2). It can be used in a wide range of applications such as waterproof coatings, biomedicine and flexible electronics, which provides a new idea for the future direction of multifunctional materials.
Fluorogenic Monitoring of α‐Amylase in Human Urine for Straightforward Diagnosis of Pancreatic Diseases
Authors: Choi Haemin , Kim Seoyun , Park Taemin , Lee Seoung Ho
Published: July 2024

In this study, we developed a sensitive method for monitoring α‐amylase using a fluorogenic approach based on the host‐guest complexation between an amphiphilic pyrenyl derivative (1) and γ‐cyclodextrins (γ‐CDs). The compound 1 self‐assembles into nanofibrils in aqueous solutions. Upon the introduction of γ‐CD, compound 1 forms an inclusion complex with it. This complex then participates in the formation of a 2 : 2 complex with another complex, leading to strong excimer fluorescence. Upon interaction with α‐amylase, γ‐CD undergoes hydrolysis, leading to the regeneration of nanofibrils, which is accompanied by a decrease in excimer fluorescence and an increase in monomeric fluorescence. This ratiometric fluorescence color change enables the sensitive detection of low levels of α‐amylase in human urine, offering a practical approach for early screening of pancreatic‐related diseases.
Additional treatment after primary conservative treatment in patients with chronic subdural hematoma—A retrospective study
Authors: Fakhry Rahman , Dirven Clemens M. F. , Moudrous Walid , Droger S. Mirjam , Asahaad Nabil , de Brabander Christiaan , Lingsma Hester F. , van der Gaag Niels A. , Hertog Heleen M. den , Jacobs Bram , Jellema Korné , Dammers Ruben , Holl Dana C.
Published: July 2024

Objective

Chronic subdural hematoma (CSDH) is a common neurological condition and is typically treated with burr hole craniostomy. Nevertheless, conservative treatment may lead to spontaneous hematoma resolution in some patients. This study aims to describe the characteristics of patients who were treated conservatively without the eventual need for additional treatment.

Methods

Data were retrospectively collected from patients who were primarily treated conservatively in three hospitals in the Netherlands from 2008 to 2018. The Primary outcome was the nonnecessity of additional treatment within 3 months after the initial CSDH diagnosis. We used univariable and multivariable logistic regression analyses to identify factors associated with not receiving additional treatment.

Results

In this study, 83 patients were included and 61 patients (73%) did not receive additional treatment within 3 months. Upon first presentation, the patients had a Markwalder Grading Scale score (MGS) of 0 (n = 5, 6%), 1 (n = 43, 52%), and 2 (n = 35, 42%). Additional treatment was less often received by patients with smaller hematoma volumes (adjusted odds ratio [aOR] 0.78 per 10 mL; 95% confidence interval [CI] 0.64–0.92). Patients using antithrombotic medication also received less additional treatment, but this association was not significant (aOR 2.02; 95% CI 0.61–6.69).

Conclusions

Three quarters of the initially conservatively treated CSDH patients do not receive additional management. Typically, these patients have smaller hematoma volumes. Further, prospective research is needed to distinguish which patients require surgical intervention and in whom primary conservative treatment suffices.
The protective effects of repetitive transcranial magnetic stimulation with different high frequencies on motor functions in MPTP/probenecid induced Parkinsonism mouse models
Authors: Lyu Zhimai , Xiao Guodong , Xie Dingyi , Huang Dandan , Chen Yanjun , Wu Chunmei , Lai Yanwei , Song Zitan , Huang Lijuan , Ming Hui , Jiang Yichen , Wang Jinwei , Chen Rixin , Luo Weifeng
Published: July 2024

Background

High‐frequency repeated transcranial magnetic stimulation (rTMS) stimulating the primary motor cortex (M1) is an alternative, adjunctive therapy for improving the motor symptoms of Parkinson's disease (PD). However, whether the high frequency of rTMS positively correlates to the improvement of motor symptoms of PD is still undecided. By controlling for other parameters, a disease animal model may be useful to compare the neuroprotective effects of different high frequencies of rTMS.

Objective

The current exploratory study was designed to compare the protective effects of four common high frequencies of rTMS (5, 10, 15, and 20 Hz) and iTBS (a special form of high‐frequency rTMS) and explore the optimal high‐frequency rTMS on an animal PD model.

Methods

Following high frequencies of rTMS application (twice a week for 5 weeks) in a MPTP/probenecid‐induced chronic PD model, the effects of the five protocols on motor behavior as well as dopaminergic neuron degeneration levels were identified. The underlying molecular mechanisms were further explored.

Results

We found that all the high frequencies of rTMS had protective effects on the motor functions of PD models to varying degrees. Among them, the 10, 15, and 20 Hz rTMS interventions induced comparable preservation of motor function through the protection of nigrostriatal dopamine neurons. The enhancement of brain‐derived neurotrophic factor (BDNF), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT‐2) and the suppression of TNF‐α and IL‐1β in the nigrostriatum were involved in the process. The efficacy of iTBS was inferior to that of the above three protocols. The effect of 5 Hz rTMS protocol was weakest.

Conclusions

Combined with the results of the present study and the possible side effects induced by rTMS, we concluded that 10 Hz might be the optimal stimulation frequency for preserving the motor functions of PD models using rTMS treatment.
The integration of circular economy and digital transformation as a catalyst for small and medium enterprise innovation
Authors: Arroyabe Marta F. , Arranz Carlos F. A. , de Arroyabe Juan Carlos Fernandez
Published: July 2024

This study examines the integration of digital and circular economy (CE) strategies in small and medium enterprises (SMEs) and their impact on innovation. The research uses data from the Eurobarometer survey conducted by the European Commission, which includes a sample of 16,365 SMEs. Using a combination of regression analysis and machine learning tools, the results indicate that a high degree of digitalisation within SMEs enhances the integration of a CE orientation. However, it is not necessary for SMEs with advanced CE orientations to have high levels of digitalisation. Additionally, the study finds variability in the integration of digital and CE orientations among SMEs, identifying four distinct groups of companies with differing levels of compatibility. Moreover, SMEs that successfully integrate both digital and CE orientations are more likely to innovate, whereas those with poor integration exhibit a lower probability of innovation. These findings offer crucial insights for managers and policymakers aiming to bolster SME innovation, digitalisation and sustainability. The research underscores the need for a balanced integration of digital and CE orientations to enhance innovation and environmental impact in SMEs.
CNS Drug Discovery in Academia: Where Basic Research Meets Innovation
Authors: Gertsch Jürg , Chicca Andrea
Published: July 2024

The involvement of academic research in drug discovery is consistently growing. However, academic projects seldom advance to clinical trials. Here, we assess the landscape of drug discovery within the National Centre of Competence in Research (NCCR) TransCure launched by the Swiss National Science Foundation to foster basic research and early‐stage drug discovery on membrane transporters. This included transporters in central nervous system (CNS) disorders, which represent a huge unmet medical need. While idea championship, sustainable funding, collaborations between disciplines at the interface of academia and industry are important for translational research, Popperian falsifiability, strong intellectual property and a motivated startup team are key elements for innovation. This is exemplified by the NCCR TransCure spin‐off company Synendos Therapeutics, a clinical stage biotech company developing the first selective endocannabinoid reuptake inhibitors (SERIs) as novel treatment for neuropsychiatric disorders. We provide a perspective on the challenges related to entering an uncharted druggable space and bridging the often mentioned “valley of death”. The high attrition rate of drug discovery projects in the CNS field within academia is often due to the lack of meaningful animal models that can provide pharmacological proof‐of‐concept for potentially disruptive technologies at the earliest stages, and the absence of solid intellectual property.
Radical total pelvic exenteration with concomitant right nephrectomy in the management of recurrent endometrioid ovarian adenocarcinoma: A case report and literature review
Authors: Ramachandran Raghavskandhan , Nistor Sabina , Gietzmann William , Symons Nicholas , Soleymani majd Hooman
Published: July 2024

Key Clinical Message

Endometrioid ovarian adenocarcinoma is a common subtype of epithelial ovarian cancer that can arise on a background of endometriosis. Maximal cytoreductive effort with an aim to remove all macroscopic disease (achieve R0) is the single independent prognostic factor for survival. Complex multidisciplinary surgeries may be required in order to achieve this.
Pulmonary tuberculosis masquerading as a mass cancer lesion: A rare case report and review of literature
Authors: Fatima Gohar , Ahmed Zafar , Akhtar Ayesha , Rehman Syed Tabish , Ali Sajjad , Anan Mahfuza
Published: July 2024

Key Clinical Message

Despite being generally treatable and preventative, pulmonary tuberculosis (PTB) is one of the most common infectious agents that cause death. Misdiagnosis of TB frequently leads to unwarranted diagnostic procedures and postpones the start of treatment.

Pulmonary tuberculosis (PTB) can present with various unusual radiological and clinical characteristics. Misdiagnosis of TB frequently leads to unwarranted diagnostic procedures and postpones the start of treatment. Here, we describe a 50‐year‐old man who presented with a cancerous‐type lesion on radiological findings and atypical symptoms that led to an initial diagnosis of lung cancer. However, histopathology and biopsy of the lung lesion revealed chronic granulomatous inflammation with caseous necrosis, confirming PTB as the true cause, with no further indications of malignancy.
Evolution of Correlated Morphological and Structural Disorder in Boehmite‐Derived Alumina with Progressive Calcination
Authors: Sudheer Nivedita , Sharna Sharmin , Rouchon Virgile , Ihiawakrim Dris , Lenertz Marc , Levitz Pierre , Rabu Pierre , Ersen Ovidiu
Published: July 2024

This study explores the morphological and structural transformation of boehmite (AlOOH) into transition aluminas during calcination, a pathway crucial for diverse industrial applications. The primary focus is on the topotactic transformation of boehmite into γ‐Al2O3 and its subsequent transitions into higher temperature polymorphs, culminating in α‐Al2O3. Utilizing a combination of in situ X‐ray diffraction, in situ and ex situ transmission electron microscopy, 27Al solid‐state nuclear magnetic resonance, thermogravimetric analysis, nitrogen physisorption, and mercury porosimetry, this work provides insights into the morphological and structural reordering during the calcination process. Furthermore, the study highlights the significant impact of thermal processing on the morphological evolution of boehmite and transition aluminas, characterized by changes in pore structure sizes and shapes. These findings offer valuable insights for optimizing the properties of alumina‐based materials for specific applications.
Unsupported Nanoporous Copper Catalyst for the Carboxylation of Terminal Alkynes with Carbon Dioxide
Authors: Xu Linxing , Wang Yunpeng , Song Jiliang , Feng Xiujuan , Wu Chaolin , Lu Wenchao , Yamamoto Yoshinori , Bao Ming
Published: July 2024

An unsupported nanoporous copper catalyst (CuNPore) with highly bicontinuous nanostructure was prepared by a chemical dealloying method. Various characterization methods were used to investigate the structure and composition of CuNPore, such as scanning electron microscopy (SEM), transmission electron microscopy (TEM), X‐ray diffraction (XRD), and X‐ray photoelectron spectroscopy (XPS). Active species of cuprous oxide were found on the surface of CuNPore catalyst. The nanoporous structure and the presence of Cu(I) enable CuNPore to catalyze the carboxylation reaction of terminal alkynes with CO2 under mild conditions. A wide range of terminal alkynes were tolerated to afford the alkynyl carboxylic acids in good to excellent yields. CuNPore catalyst can be easily recovered and recycled five times without any loss of activity.
Multi‐Catalytic Metal‐Based Homogeneous‐Heterogeneous Systems in Organic Chemistry
Authors: Arango‐Daza Juan Camilo , Rivero‐Crespo Miguel A.
Published: July 2024

The combination of metal‐based homogeneous and heterogeneous catalysts in the same reaction media is a powerful, yet relatively unexplored approach in organic chemistry. This strategy can address important limitations associated with purely homogeneous or heterogeneous catalysis such as the incompatibility of different catalytic species in solution, or the limited tunability of solid catalysts, respectively. Moreover, the facile reusability of the solid catalyst, contributes to increase the overall sustainability of the process. As a result, this semi‐heterogeneous multi‐catalytic approach has unlocked significant advances in organic chemistry, improving existing reactions and even enabling the discovery of novel transformations, exemplified by the formal alkane metathesis. This concept article aims to showcase the benefits of this strategy through the exploration of diverse relevant examples from the literature, hoping to spur research on new metal‐based homogeneous‐heterogeneous catalyst combinations that will result in reactivity challenging to achieve by conventional homogeneous or heterogeneous catalysis alone.
An Experimental Approach to Overcome the Fouling Issue in Micro Heat Exchangers
Authors: Aselmeyer Felicitas , Spiegel Christoph , Augustin Wolfgang , Scholl Stephan
Published: July 2024

Micro heat exchangers improve heat and mass transfer compared to conventional heat exchangers, enabling more energy‐efficient applications. However, their sensitivity to fouling limits broader industrial application. This approach presents a combined investigation of fouling and cleaning in microscale heat exchangers using two test rigs. Individual sets of analysis methods are developed to improve the understanding of heat and mass transfer on the microscale. In addition to known methods, such as pressure loss analysis, newly developed and established image analysis techniques are used to monitor fouling and cleaning. Based on the presented methods, it is possible to predict the initial position of thermally induced fouling and to demonstrate the applicability of automated cleaning on the microscale.
Modular Assembly of Six‐Membered Carbocyclic Spirooxindoles via Peterson Olefination/Michael Addition/C(sp3) Arylation Cascade
Authors: Jia Feng‐Cheng , Yuan Zi‐Yi , Luo Na , Gu Shuang‐Xi , Hu Xiao‐Qiang
Published: July 2024

Comprehensive Summary

Concise assembly of spirooxindoles is of great significance but a challenging task in modern organic synthesis. Described herein is an unusual base‐promoted [4+2] spiroannulation of rarely used isatin‐derived β‐silylcarbinols with o‐halogen aromatic ketones, which enables rapid and modular synthesis of six‐membered carbocyclic spirooxindoles in high yields with excellent functional group tolerance (> 50 examples). Mechanistic experiments revealed that this reaction involved a Peterson olefination, Michael addition and intramolecular C(sp3) arylation cascade. The variegated synthetic derivatization of target products and successful construction of bioactive molecules further illustrate the synthetic potential in spirooxindole‐related drug discovery.
Regulating the Photoisomerization of Covalent Organic Framework for Enhanced Photocatalytic Hydrogen Evolution†
Authors: Huang Xingye , Guo Jia
Published: July 2024

Comprehensive Summary

Covalent organic framework (COF) is a desirable platform to tailor electronic properties for improving photocatalytic performances. However, the study on excited‐state configurations that determine photogenerated carrier dynamics has long been neglected. Herein, we concentrate on the molecular design of β‐ketoenamine‐linked COFs to drive their photoisomerization via the excited‐state intra‐molecular proton transfer (ESIPT), which can induce the partial keto‐to‐enol tautomerization and accordingly rearrange the photoinduced charge distribution. We demonstrate that the push‐pull electronic effect of functional side groups attached on the framework linkers is directly correlated with the ESIPT process. The phenylene linkers modified with electron‐withdrawing cyano‐groups reinforce the ESIPT‐induced tautomerization, leading to the in situ partial enolization for extended π‐conjugation and rearranged electron‐hole distribution. In contrast, the electron‐rich linkers limit the photoisomerization of COF and suppress the photoinduced electron accumulation. Thus, the maximum hydrogen evolution rate is achieved by the cyano‐modified COF, reaching as high as 162.72 mmol·g–1·h–1 with an apparent quantum efficiency of 13.44% at 475 nm, which is almost 11.5‐fold higher than those of analogous COFs with electron‐rich linkers. Our work opens up an avenue to control over the excited‐state structure transformation for enhanced photochemical applications.
Fluorescein Isothiocyanate Labelled PCL‐PEG‐PCL Copolymer as Delivery System of Capsaicin
Authors: Ferrentino Nancy , Mariastella Caputo Tania , Cusano Angela Maria , Aliberti Anna , Cusano Andrea , Pappalardo Daniela
Published: July 2024

Amphiphilic block copolymers, made of biocompatible polycaprolactone (PCL) and polyethylene glycol (PEG), due to their ability to self‐assemble in water into nanoscopic micelles, have been largely exploited for drug delivery systems (DDS). This study introduces a novel approach by synthesizing a fluorescein isothiocyanate FITC‐labelled PCL‐PEG‐PCL triblock copolymer, with the aim to develop a drug delivery system for natural bioactive. As a proof of concept, the FITC‐labelled PCL‐PEG‐PCL copolymer is applied for the preparation of micelles encapsulating into the core capsaicin (CP), a pungent alkaloid found in chili peppers with diverse therapeutic applications. Challenges associated with CP′s solubility, bioavailability, and stability are addressed using this DDS. Comprehensive characterization of FITC‐labelled copolymer is conducted using a range of analytical techniques, including nuclear magnetic resonance (NMR), dynamic light scattering (DLS), high‐performance liquid chromatography (HPLC), Fourier‐transform infrared spectroscopy (FTIR), fluorescence, and confocal laser scanning microscopy (CLSM). Key properties such as critical micelle concentration, CP loading, and release behavior are thoroughly investigated and compared with the characteristics of the unlabeled parent copolymer. This research pioneers the investigation of PCL‐PEG‐PCL triblock copolymers for CP delivery, along with the use of FITC‐labelled variants, opening new avenues for research in drug delivery and nanomedicine.
Techniques for improving the specificity of sandwich enzyme‐linked immunosorbent assay‐based drug screening
Authors: Steel Rohan , Botteon Antony , Timms Mark
Published: July 2024

ELISA assays are commonly used for drug screening by racing laboratories but are known to suffer from limited specificity. Inaccurate ELISA screening results are typically produced by non‐specific antibody interactions or by the retention of chromogenic material in the sample well due to sample degradation. While confirmation of drug positives can be achieved by mass spectrometry, the follow‐up of inaccurate ELISA screening results represents an unnecessary cost in staff time and reagents. This is particularly true in the case of rhEPO screening using sandwich ELISA assays, where the confirmation method requires up to 3 days to perform. While most racing laboratories purchase commercial ELISA kits, these products can be customised to provide increased specificity for enhanced screening of positive samples. The specificity of commercial sandwich ELISA kits can be improved by a variety of mechanisms including the addition of competing analyte specific antibodies, substitution of capture antibodies or by performing ELISA analysis with and without capture antibodies. Non‐specific signals in difficult matrices such as canine urine can also be reduced by the addition of BSA solutions to the ELISA plate prior to the addition of samples.
Exploring depth‐related patterns of sponge diversity and abundance in marginal reefs
Authors: Morais Juliano , Cordeiro Igor L. , Medeiros Aline P. M. , Santos George G. , Santos Bráulio A.
Published: July 2024

Marine sponges play a vital role in the reef's benthic community; however, understanding how their diversity and abundance vary with depth is a major challenge, especially on marginal reefs in areas deeper than 30 m. To help bridge this gap, we used underwater videos at 24 locations between 2‐ and 62‐meter depths on a marginal reef system in the Southwestern Atlantic to investigate the effect of depth on the sponge metacommunity. Specifically, we quantified the abundance, density, and taxonomic composition of sponge communities, and decomposed their gamma (γ) diversity into alpha (α) and beta (β) components. We also assessed whether beta diversity was driven by species replacement (turnover) or by nesting of local communities (nestedness). We identified 2020 marine sponge individuals, which belong to 36 species and 24 genera. As expected, deep areas (i.e., those greater than 30 m) presented greater sponge abundance and more than eightfold the number of sponges per square meter compared to shallow areas. About 50% of the species that occurred in shallow areas (<30 m) also occurred in deep areas. Contrarily to expectations, alpha diversity of rare (0Dα), typical (1Dα), or dominant (2Dα) species did not vary with depth, but the shallow areas had greater beta diversity than the deep ones, especially for typical (1Dβ) and dominant (2Dβ) species. Between 92.7% and 95.7% of the beta diversity was given by species turnover both inside and between shallow and deep areas. Our results support previous studies that found greater sponge abundance and density in deep areas and reveal that species sorting is stronger at smaller depths, generating more beta diversity across local communities in shallow than deep areas. Because turnover is the major driver at any depth, the entire depth gradient should be considered in management and conservation strategies.
Revisiting Wolbachia detections: Old and new issues in Aedes aegypti mosquitoes and other insects
Authors: Ross Perran A. , Hoffmann Ary A.
Published: July 2024

Wolbachia continue to be reported in species previously thought to lack them, particularly Aedes aegypti mosquitoes. The presence of Wolbachia in this arbovirus vector is considered important because releases of mosquitoes with transinfected Wolbachia are being used around the world to suppress pathogen transmission and these efforts depend on a lack of Wolbachia in natural populations of this species. We previously assessed papers reporting Wolbachia in natural populations of Ae. aegypti and found little evidence that seemed convincing. However, since our review, more and more papers are emerging on Wolbachia detections in this species. Our purpose here is to evaluate these papers within the context of criteria we previously established but also new criteria that include the absence of releases of transinfections within the local areas being sampled which has contaminated natural populations in at least one case where novel detections have been reported. We also address the broader issue of Wolbachia detection in other insects where similar issues may arise which can affect overall estimates of this endosymbiont more generally. We note continuing shortcomings in papers purporting to find natural Wolbachia in Ae. aegypti which are applicable to other insects as well.
Far away from home? Ancient DNA shows the presence of bicolored shrew (Crocidura leucodon) in Bronze Age Denmark
Authors: Mousavi‐Derazmahalleh Mahsa , Haue Niels , Kanstrup Marie , Laursen Jørgen T. , Lukehurst Sherralee S. , Kveiborg Jacob , Allentoft Morten E.
Published: July 2024

An excavation of an Early Iron Age village near Aalborg in Denmark uncovered the jaws and skull fragments from a small mammal that were morphologically identified to the genus Crocidura (white‐toothed shrews). Three Crocidura species are known from prehistoric continental Europe but none of them are distributed in Scandinavia, which is why this surprising finding warranted further analyses. The bone was radiocarbon‐dated to 2840–2750 calibrated years before present (cal. BP), corresponding to the Late Bronze Age and hence earlier than the Iron Age archeological context in which it was found. Using highly optimized ancient DNA protocols, we extracted DNA from one tooth and shotgun‐sequenced the sample to reconstruct a near‐complete mitochondrial reference genome (17,317 bp, 32.6× coverage). Phylogenetic analyses determined this specimen as a bicolored shrew (Crocidura leucodon) but with a phylogenetic position basal to the clade of known sequences from this species. The confirmation of Crocidura presence in Denmark by the Late Bronze Age sheds new light on the prehistoric natural history of Scandinavia. We discuss the implications of this finding from both zoo‐archeological and ecological perspectives. Furthermore, the mitochondrial genome reconstructed in this study offers a valuable resource for future research exploring the genetic makeup and evolutionary history of Eurasian shrew populations.
How to find a wolverine: Factors affecting detection at wolverine (Gulo gulo) bait stations in western Canada
Authors: Kortello Andrea , Hausleitner Doris , Mowat Garth , Barrueto Mirjam , Heim Nicole , Larson Lisa , Lucid Michael , Clevenger Anthony
Published: July 2024

High individual detection success enables precise estimates of density and the ability to monitor trends in abundance for wolverine and other low‐density species, information that is critical for the implementation and assessment of conservation measures. We evaluated a dataset that included six different wolverine capture–recapture studies over a large gradient in wolverine (Gulo gulo) density to provide recommendations for increasing detection. We examined factors related to bait station components, habitat, and seasonal timing. Accounting for variation in wolverine density and trap duration, our results suggest that bait stations setups having a run pole, frame, and camera to photograph unique ventral color patterns, in addition to hair snag devices, identify more individual wolverine than those without. The presence of snow is a habitat feature that also increases individual detection. Female detection rates were lower than male detection rates at the onset of the reproductive denning season in late February and early March compared with January and early February. We found latency to detection was independent of wolverine density, but greater in areas with human influence. Relatively high rates of genotyping success (55%) were predicted by even a single guard hair left at bait stations, while underfur required ~15 hairs for similar success. Longer sampling intervals reduced genotyping success in spring, more so for underfur than guard hair. Hair samples acquired from barbwire were of higher quality than those from either alligator clips or gun brushes. To improve individual detection for wolverine inventory and monitoring, we recommend deploying run pole setups in areas with low human disturbance that will retain snow into late spring. Extending the winter trapping effort into April and May could increase the chances of detecting denning females. Latency to detection suggests that traps should be active for more than a month, especially in human‐influenced areas, but genotyping success suggests that traps should also be cleared of hair samples at smaller intervals of a month or less, during late winter/spring.
How can geomorphology facilitate a better understanding of glacier and ice sheet behaviour?
Authors: Jones Richard S. , Miller Lauren E. , Westoby Matthew J.
Published: July 2024

Glaciers and ice sheets are an integral part of Earth's system, advancing and retreating in response to changes in climate. Clues about the past, present and future behaviour of these ice masses are found throughout current and former glaciated landscapes. In this commentary, we outline recent scientific advances from a collection of articles in which geomorphological evidence is used to inform us about the behaviour of glaciers and ice sheets across a range of spatial (landform to continent) and temporal (seasons to millennia) scales. Through a diversity of approaches including field measurements, remote sensing and numerical modelling, these studies build on an extensive background literature to deepen our understanding of how ice flows, how glaciers and ice sheets respond to climate change, and of the processes of ice advance and retreat and the stability of the system. Further integration of knowledge across the fields of geomorphology and glaciology will have tangible benefits for managing the societal and environmental impacts of glacier change and for improved projections of sea‐level rise over the coming decades to centuries.