bluuebunny/crossref_metadata_2025 huggingface dataset:
De novo variants underlying monogenic syndromes with intellectual disability in a neurodevelopmental cohort from India
Authors: Pande Shruti , Majethia Purvi , Nair Karthik , Rao Lakshmi Priya , Mascarenhas Selinda , Kaur Namanpreet , do Rosario Michelle C. , Neethukrishna Kausthubham , Chaurasia Ankur , Hunakunti Bhagesh , Jadhav Nalesh , Xavier Sruthy , Kumar Jeevan , Bhat Vivekananda , Bhavani Gandham SriLakshmi , Narayanan Dhanya Lakshmi , Yatheesha B. L. , Patil Siddaramappa J. , Nampoothiri Sheela , Kamath Nutan , Aroor Shrikiran , Bhat Y Ramesh , Lewis Leslie E. , Sharma Suvasini , Bajaj Shruti , Sankhyan Naveen , Siddiqui Shahyan , Nayak Shalini S. , Bielas Stephanie , Girisha Katta Mohan , Shukla Anju
Published: December 2023

The contribution of de novo variants as a cause of intellectual disability (ID) is well established in several cohorts reported from the developed world. However, the genetic landscape as well as the appropriate testing strategies for identification of de novo variants of these disorders remain largely unknown in low-and middle-income countries like India. In this study, we delineate the clinical and genotypic spectrum of 54 families (55 individuals) with syndromic ID harboring rare de novo variants. We also emphasize on the effectiveness of singleton exome sequencing as a valuable tool for diagnosing these disorders in resource limited settings. Overall, 46 distinct disorders were identified encompassing 46 genes with 51 single-nucleotide variants and/or indels and two copy-number variants. Pathogenic variants were identified in CREBBP, TSC2, KMT2D, MECP2, IDS, NIPBL, NSD1, RIT1, SOX10, BRWD3, FOXG1, BCL11A, KDM6B, KDM5C, SETD5, QRICH1, DCX, SMARCD1, ASXL1, ASXL3, AKT3, FBN2, TCF12, WASF1, BRAF, SMARCA4, SMARCA2, TUBG1, KMT2A, CTNNB1, DLG4, MEIS2, GATAD2B, FBXW7, ANKRD11, ARID1B, DYNC1H1, HIVEP2, NEXMIF, ZBTB18, SETD1B, DYRK1A, SRCAP, CASK, L1CAM, and KRAS. Twenty-four of these monogenic disorders have not been previously reported in the Indian population. Notably, 39 out of 53 (74%) disease-causing variants are novel. These variants were identified in the genes mainly encoding transcriptional and chromatin regulators, serine threonine kinases, lysosomal enzymes, molecular motors, synaptic proteins, neuronal migration machinery, adhesion molecules, structural proteins and signaling molecules.
Precise control over gas-transporting channels in zeolitic imidazolate framework glasses
Authors: Smirnova Oksana , Hwang Seungtaik , Sajzew Roman , Ge Lingcong , Reupert Aaron , Nozari Vahid , Savani Samira , Chmelik Christian , Reithofer Michael R. , Wondraczek Lothar , Kärger Jörg , Knebel Alexander
Published: December 2023

Porous metal–organic frameworks have emerged to resolve important challenges of our modern society, such as CO2 sequestration. Zeolitic imidazolate frameworks (ZIFs) can undergo a glass transition to form ZIF glasses; they combine the liquid handling of classical glasses with the tremendous potential for gas separation applications of ZIFs. Using millimetre-sized ZIF-62 single crystals and centimetre-sized ZIF-62 glass, we demonstrate the scalability and processability of our materials. Further, following the evolution of gas penetration into ZIF crystals and ZIF glasses by infrared microimaging techniques, we determine the diffusion coefficients and changes to the pore architecture on the ångström scale. The evolution of the material on melting and processing is observed in situ on different length scales by using a microscope-coupled heating stage and analysed microstructurally by transmission electron microscopy. Pore collapse during glass processing is further tracked by changes in the volume and density of the glasses. Mass spectrometry was utilized to investigate the crystal-to-glass transition and thermal-processing ability. The controllable tuning of the pore diameter in ZIF glass may enable liquid-processable ZIF glass membranes for challenging gas separations.
Autonomous chemical research with large language models
Authors: Boiko Daniil A. , MacKnight Robert , Kline Ben , Gomes Gabe
Published: December 2023

Transformer-based large language models are making significant strides in various fields, such as natural language processing1–5, biology6,7, chemistry8–10 and computer programming11,12. Here, we show the development and capabilities of Coscientist, an artificial intelligence system driven by GPT-4 that autonomously designs, plans and performs complex experiments by incorporating large language models empowered by tools such as internet and documentation search, code execution and experimental automation. Coscientist showcases its potential for accelerating research across six diverse tasks, including the successful reaction optimization of palladium-catalysed cross-couplings, while exhibiting advanced capabilities for (semi-)autonomous experimental design and execution. Our findings demonstrate the versatility, efficacy and explainability of artificial intelligence systems like Coscientist in advancing research.
Cytoneme-mediated transport of active Wnt5b–Ror2 complexes in zebrafish
Authors: Zhang Chengting , Brunt Lucy , Ono Yosuke , Rogers Sally , Scholpp Steffen
Published: December 2023

Chemical signalling is the primary means by which cells communicate in the embryo. The underlying principle refers to a group of ligand-producing cells and a group of cells that respond to this signal because they express the appropriate receptors1,2. In the zebrafish embryo, Wnt5b binds to the receptor Ror2 to trigger the Wnt–planar cell polarity (PCP) signalling pathway to regulate tissue polarity and cell migration3,4. However, it remains unclear how this lipophilic ligand is transported from the source cells through the aqueous extracellular space to the target tissue. In this study, we provide evidence that Wnt5b, together with Ror2, is loaded on long protrusions called cytonemes. Our data further suggest that the active Wnt5b–Ror2 complexes form in the producing cell and are handed over from these cytonemes to the receiving cell. Then, the receiving cell has the capacity to initiate Wnt–PCP signalling, irrespective of its functional Ror2 receptor status. On the tissue level, we further show that cytoneme-dependent spreading of active Wnt5b–Ror2 affects convergence and extension in the zebrafish gastrula. We suggest that cytoneme-mediated transfer of ligand–receptor complexes is a vital mechanism for paracrine signalling. This may prompt a reevaluation of the conventional concept of characterizing responsive and non-responsive tissues solely on the basis of the expression of receptors.
The PfRCR complex bridges malaria parasite and erythrocyte during invasion
Authors: Farrell Brendan , Alam Nawsad , Hart Melissa N. , Jamwal Abhishek , Ragotte Robert J. , Walters-Morgan Hannah , Draper Simon J. , Knuepfer Ellen , Higgins Matthew K.
Published: December 2023

The symptoms of malaria occur during the blood stage of infection, when parasites invade and replicate within human erythrocytes. The PfPCRCR complex1, containing PfRH5 (refs. 2,3), PfCyRPA, PfRIPR, PfCSS and PfPTRAMP, is essential for erythrocyte invasion by the deadliest human malaria parasite, Plasmodium falciparum. Invasion can be prevented by antibodies3–6 or nanobodies1 against each of these conserved proteins, making them the leading blood-stage malaria vaccine candidates. However, little is known about how PfPCRCR functions during invasion. Here we present the structure of the PfRCR complex7,8, containing PfRH5, PfCyRPA and PfRIPR, determined by cryogenic-electron microscopy. We test the hypothesis that PfRH5 opens to insert into the membrane9, instead showing that a rigid, disulfide-locked PfRH5 can mediate efficient erythrocyte invasion. We show, through modelling and an erythrocyte-binding assay, that PfCyRPA-binding antibodies5 neutralize invasion through a steric mechanism. We determine the structure of PfRIPR, showing that it consists of an ordered, multidomain core flexibly linked to an elongated tail. We also show that the elongated tail of PfRIPR, which is the target of growth-neutralizing antibodies6, binds to the PfCSS–PfPTRAMP complex on the parasite membrane. A modular PfRIPR is therefore linked to the merozoite membrane through an elongated tail, and its structured core presents PfCyRPA and PfRH5 to interact with erythrocyte receptors. This provides fresh insight into the molecular mechanism of erythrocyte invasion and opens the way to new approaches in rational vaccine design.
Mitochondrial dysfunction abrogates dietary lipid processing in enterocytes
Authors: Moschandrea Chrysanthi , Kondylis Vangelis , Evangelakos Ioannis , Herholz Marija , Schneider Farina , Schmidt Christina , Yang Ming , Ehret Sandra , Heine Markus , Jaeckstein Michelle Y. , Szczepanowska Karolina , Schwarzer Robin , Baumann Linda , Bock Theresa , Nikitopoulou Efterpi , Brodesser Susanne , Krüger Marcus , Frezza Christian , Heeren Joerg , Trifunovic Aleksandra , Pasparakis Manolis
Published: December 2023

Digested dietary fats are taken up by enterocytes where they are assembled into pre-chylomicrons in the endoplasmic reticulum followed by transport to the Golgi for maturation and subsequent secretion to the circulation1. The role of mitochondria in dietary lipid processing is unclear. Here we show that mitochondrial dysfunction in enterocytes inhibits chylomicron production and the transport of dietary lipids to peripheral organs. Mice with specific ablation of the mitochondrial aspartyl-tRNA synthetase DARS2 (ref. 2), the respiratory chain subunit SDHA3 or the assembly factor COX10 (ref. 4) in intestinal epithelial cells showed accumulation of large lipid droplets (LDs) in enterocytes of the proximal small intestine and failed to thrive. Feeding a fat-free diet suppressed the build-up of LDs in DARS2-deficient enterocytes, which shows that the accumulating lipids derive mostly from digested fat. Furthermore, metabolic tracing studies revealed an impaired transport of dietary lipids to peripheral organs in mice lacking DARS2 in intestinal epithelial cells. DARS2 deficiency caused a distinct lack of mature chylomicrons concomitant with a progressive dispersal of the Golgi apparatus in proximal enterocytes. This finding suggests that mitochondrial dysfunction results in impaired trafficking of chylomicrons from the endoplasmic reticulum to the Golgi, which in turn leads to storage of dietary lipids in large cytoplasmic LDs. Taken together, these results reveal a role for mitochondria in dietary lipid transport in enterocytes, which might be relevant for understanding the intestinal defects observed in patients with mitochondrial disorders5.
Minute-scale oscillatory sequences in medial entorhinal cortex
Authors: Gonzalo Cogno Soledad , Obenhaus Horst A. , Lautrup Ane , Jacobsen R. Irene , Clopath Claudia , Andersson Sebastian O. , Donato Flavio , Moser May-Britt , Moser Edvard I.
Published: December 2023

The medial entorhinal cortex (MEC) hosts many of the brain’s circuit elements for spatial navigation and episodic memory, operations that require neural activity to be organized across long durations of experience1. Whereas location is known to be encoded by spatially tuned cell types in this brain region2,3, little is known about how the activity of entorhinal cells is tied together over time at behaviourally relevant time scales, in the second-to-minute regime. Here we show that MEC neuronal activity has the capacity to be organized into ultraslow oscillations, with periods ranging from tens of seconds to minutes. During these oscillations, the activity is further organized into periodic sequences. Oscillatory sequences manifested while mice ran at free pace on a rotating wheel in darkness, with no change in location or running direction and no scheduled rewards. The sequences involved nearly the entire cell population, and transcended epochs of immobility. Similar sequences were not observed in neighbouring parasubiculum or in visual cortex. Ultraslow oscillatory sequences in MEC may have the potential to couple neurons and circuits across extended time scales and serve as a template for new sequence formation during navigation and episodic memory formation.
Emergence of replication timing during early mammalian development
Authors: Nakatani Tsunetoshi , Schauer Tamas , Altamirano-Pacheco Luis , Klein Kyle N. , Ettinger Andreas , Pal Mrinmoy , Gilbert David M. , Torres-Padilla Maria-Elena
Published: December 2023

DNA replication enables genetic inheritance across the kingdoms of life. Replication occurs with a defined temporal order known as the replication timing (RT) programme, leading to organization of the genome into early- or late-replicating regions. RT is cell-type specific, is tightly linked to the three-dimensional nuclear organization of the genome1,2 and is considered an epigenetic fingerprint3. In spite of its importance in maintaining the epigenome4, the developmental regulation of RT in mammals in vivo has not been explored. Here, using single-cell Repli-seq5, we generated genome-wide RT maps of mouse embryos from the zygote to the blastocyst stage. Our data show that RT is initially not well defined but becomes defined progressively from the 4-cell stage, coinciding with strengthening of the A and B compartments. We show that transcription contributes to the precision of the RT programme and that the difference in RT between the A and B compartments depends on RNA polymerase II at zygotic genome activation. Our data indicate that the establishment of nuclear organization precedes the acquisition of defined RT features and primes the partitioning of the genome into early- and late-replicating domains. Our work sheds light on the establishment of the epigenome at the beginning of mammalian development and reveals the organizing principles of genome organization.
Sudden death in young South European population: a cross-sectional study of postmortem cases
Authors: Carrington Mafalda , de Gouveia Rosa Henriques , Teixeira Rogério , Corte-Real Francisco , Gonçalves Lino , Providência Rui
Published: December 2023

To describe the annual incidence and the leading causes of sudden non-cardiac and cardiac death (SCD) in children and young adult Portuguese population. We retrospectively reviewed autopsy of sudden unexpected deaths reports from the Portuguese National Institute of Legal Medicine and Forensic Sciences’ database, between 2012 and 2016, for the central region of Portugal, Azores and Madeira (ages 1–40: 26% of the total population). During a 5-year period, 159 SD were identified, corresponding to an annual incidence of 2,4 (95%confidence interval, 1,5–3,6) per 100.000 people-years. Victims had a mean age of 32 ± 7 years-old, and 72,3% were male. There were 70,4% cardiac, 16,4% respiratory and 7,5% neurologic causes of SD. The most frequent cardiac anatomopathological diagnosis was atherosclerotic coronary artery disease (CAD) (33,0%). There were 15,2% victims with left ventricular hypertrophy, with a diagnosis of hypertrophic cardiomyopathy only possible in 2,7%. The prevalence of cardiac pathological findings of uncertain significance was 30,4%. In conclusion, the annual incidence of SD was low. Atherosclerotic CAD was diagnosed in 33,0% victims, suggesting the need to intensify primary prevention measures in the young. The high prevalence of pathological findings of uncertain significance emphasizes the importance of molecular autopsy and screening of first-degree relatives.
Psychological distress and voting behaviour in nine countries of the former Soviet Union
Authors: Stickley Andrew , Sumiyoshi Tomiki , Kondo Naoki , Leinsalu Mall , Inoue Yosuke , Ruchkin Vladislav , Shin Jae Il , McKee Martin
Published: December 2023

Poorer mental health is linked to a lower likelihood of voting in elections. However, little is known about this association in non-Western settings. This study examined the association between psychological distress and voting in nine countries of the former Soviet Union (FSU). Data were analysed from 18,000 respondents aged ≥ 18 in Armenia, Azerbaijan, Belarus, Georgia, Moldova, Kazakhstan, Kyrgyzstan, Russia and Ukraine collected during the Health in Times of Transition (HITT) survey in 2010/11. Information was collected on previous voting behaviour and future voting intentions. Psychological distress was assessed with a 12-item scale. In pooled multivariable logistic regression analyses psychological distress was significantly associated with ‘never voting’ (not having voted previously or intending to vote in future) and ‘past voting only’ (having voted previously but not intending to vote in future). In stratified analyses psychological distress was linked to never voting in women and working-age adults. The significant association between psychological distress and voting was observed only in hybrid political regimes. Psychological distress is associated with a reduced likelihood of voting in FSU countries especially among women, working-age adults and those in hybrid political regimes.
Preparation and characterization of a curcumin nanoemulsion gel for the effective treatment of mycoses
Authors: Al Fatease Adel , Alqahtani Ali , Khan Barkat A. , Mohamed Jamal Moideen Muthu , Farhana Syeda Ayesha
Published: December 2023

Fungal infections of skin including mycoses are one of the most common infections in skin or skins. Mycosis is caused by dermatophytes, non-dermatophyte moulds and yeasts. Various studies show different drugs to treat mycoses, yet there is need to treat it with applied drugs delivery. This study was designed to prepare a bio curcumin (CMN) nanoemulsion (CMN-NEs) for transdermal administration to treat mycoses. The self-nanoemulsification approach was used to prepare a nanoemulsion (NE), utilizing an oil phase consisting of Cremophor EL 100 (Cre EL), glyceryl monooleate (GMO), and polyethylene glycol 5000 (PEG 5000). Particle size (PS), polydispersity index (PDI), zeta potential (ZP), Fourier transform infrared (FTIR) spectrophotometric analysis, and morphological analyses were performed to evaluate the nanoemulsion (NE). The in vitro permeation of CMN was investigated using a modified vertical diffusion cell with an activated dialysis membrane bag. Among all the formulations, a stable, spontaneously produced nanoemulsion was determined with 250 mg of CMN loaded with 10 g of the oil phase. The average droplet size, ZP, and PDI of CMN-NEs were 90.0 ± 2.1 nm, − 7.4 ± 0.4, and 0.171 ± 0.03 mV, respectively. The release kinetics of CMN differed from zero order with a Higuchi release profile as a result of nanoemulsification, which also significantly increased the flux of CMN permeating from the hydrophilic matrix gel. Overall, the prepared nanoemulsion system not only increased the permeability of CMN but also protected it against chemical deterioration. Both CMN-ME (24.0 ± 0.31 mm) and CMN-NE gel (29.6 ± 0.25 mm) had zones of inhibition against Candida albicans that were significantly larger than those of marketed Itrostred gel (21.5 ± 0.34 mm). The prepared CMN-NE improved the bioavailability, better skin penetration, and the CMN-NE gel enhanced the release of CMN from the gel matrix on mycotic patients.
Association between reduced left ventricular ejection fraction and peritoneal dialysis related peritonitis: a single center retrospective cohort study in Japan
Authors: Yamaguchi Makoto , Obayashi Takaaki , Kobayashi Naoto , Izumi Naoki , Nagai Masaaki , Nobata Hironobu , Asai Akimasa , Kamiya Keisuke , Sugiyama Hirokazu , Kinashi Hiroshi , Banno Shogo , Ando Masahiko , Imaizumi Takahiro , Kubo Yoko , Katsuno Takayuki , Ishimoto Takuji , Ito Yasuhiko
Published: December 2023

We present a single-center retrospective analysis of 228 Japanese patients with peritoneal dialysis, in which we examined whether reduced left ventricular ejection fraction (LVEF) is a risk factor for peritonitis development. Time-dependent multivariable-adjusted Cox proportional hazards models revealed that reduced LVEF (LVEF < 50% vs. preserved LVEF ≥ 50%, hazard ratio (HR) 2.10; 95% confidence interval (CI) 1.16–3.82) was associated with peritonitis. Qualitatively, similar associations with reduced LVEF (< 50%) were observed for enteric peritonitis (adjusted HR 7.68; 95% CI 2.51–23.5) but not for non-enteric peritonitis (adjusted HR 1.15; 95% CI 0.54–2.44). Reduced LVEF is associated with a significantly higher risk of subsequent peritonitis, particularly enteric peritonitis. These results indicate that patients with reduced LVEF may be at risk of enteric peritonitis from bowel sources caused by intestinal involvement due to cardiac dysfunction.
Analysis of factors associated with delayed diagnosis and treatment of testicular torsion in 1005 cases from Chongqing city, China: a cross-sectional study
Authors: Yi Hongmei , Wang Delin , Wu Xiaohou , Gan Xiangzhi , Wang Dan , zhao Xin , Cheng Honglin
Published: December 2023

This study aimed to investigate the clinical and social factors of delayed treatment for testicular torsion (TT) and to explore the risk factors of testicular excision in China. The clinical data of 1005 patients with TT who were admitted to 48 medical institutions in Chongqing city (China) from January 2012 to December 2021 were retrospectively analyzed. It was revealed that the misdiagnosis rates of non-senior (junior and middle) grade doctors and senior doctors were 25.1% and 9.6%, respectively. The proportion of TT patients who received timely treatment (within 6 h after onset of symptoms) was 23.8%. The results of the multivariable logistic regression analysis indicated that absent cremasteric reflex was a protective factor for delayed surgery of more than 6 h from onset of symptoms to surgery. Misdiagnosis, consultation with a non-urologist as the first consultant doctor, absence blood flow in color Doppler ultrasound, negative high-riding testis findings, the presence of fever, and non-manual detorsion were identified as risk factors associated with delayed surgery (more than 6 h from the onset of symptoms) for TT. Furthermore, misdiagnosis, non-urologist first-consultant doctor, absent blood flow in DUS, non-manual detorsion, fever, degree of cord twisting > 180, and the initial diagnosis in tertiary hospitals were risk factors for orchidectomy. Having TT on the right side, and the presence of nausea and vomiting were identified as protective factors for orchidectomy. Technical training in the diagnosis and treatment of TT should be extended to primary hospitals and doctors to significantly improve their accuracy in managing this condition.
A neural network computational structure for the fractional order breast cancer model
Authors: Huang Zhenglin , Haider Qusain , Sabir Zulqurnain , Arshad Mubashar , Siddiqui Bushra Khatoon , Alam Mohammad Mahtab
Published: December 2023

The current study provides the numerical performances of the fractional kind of breast cancer (FKBC) model, which are based on five different classes including cancer stem cells, healthy cells, tumor cells, excess estrogen, and immune cells. The motive to introduce the fractional order derivatives is to present more precise solutions as compared to integer order. A stochastic computing reliable scheme based on the Levenberg Marquardt backpropagation neural networks (LMBNNS) is proposed to solve three different cases of the fractional order values of the FKBC model. A designed dataset is constructed by using the Adam solver in order to reduce the mean square error by taking the data performances as 9% for both testing and validation, while 82% is used for training. The correctness of the solver is approved through the negligible absolute error and matching of the solutions for each model’s case. To validates the accuracy, and consistency of the solver, the performances based on the error histogram, transition state, and regression for solving the FKBC model.
Safety of using a large femoral head on thin polyethylene for total hip arthroplasty based on different types of polyethylene
Authors: Do Min Uk , Moon Nam Hoon , Suh Kuen Tak , Kim Jung Shin , Lee Sang-Min , Shin Won Chul
Published: December 2023

The use of a large femoral head in total hip arthroplasty (THA) to stabilize and reduce the incidence of dislocation is on the increase, but concerns arise when combining them with small acetabular components due to potential mechanical failures in thin polyethylene (PE) liners. A single-institution, retrospective cohort study was conducted on 116 patients with minimum 2-year follow-up who received 36-mm femoral heads and acetabular components ≤ 52 mm, using either remelted highly cross-linked polyethylene (remelted HXLPE) or vitamin E-infused HXLPE (VEPE). Osteolysis and implant loosening were not observed in either group. Although a fracture of the PE liner was observed in each group (1.7%), the clinical outcomes were excellent, as the mean modified Harris Hip Score (mHHS) at the last follow-up was 93.5. Moreover, the mean linear wear rates measured by digital imaging software in both groups were low, with 0.035 mm/y in remelted HXLPE and 0.030 mm/y in VEPE. In conclusion, The use of a large femoral head on a thin PE liner can be a viable treatment option in patients who need to prioritize stability; however, careful attention should be paid to mechanical fractures of the PE liner.
Cell cycle-dependent activation of proneural transcription factor expression and reactive gliosis in rat Müller glia
Authors: Nishino Reiko , Nomura-Komoike Kaori , Iida Tomohiro , Fujieda Hiroki
Published: December 2023

Retinal Müller glia have a capacity to regenerate neurons in lower vertebrates like zebrafish, but such ability is extremely limited in mammals. In zebrafish, Müller glia proliferate after injury, which promotes their neurogenic reprogramming while inhibiting reactive gliosis. In mammals, however, how the cell cycle affects the fate of Müller glia after injury remains unclear. Here, we focused on the expression of proneural transcription factors, Ngn2 and Ascl1, and a gliosis marker glial fibrillary acidic protein (GFAP) in rat Müller glia after N-methyl-N-nitrosourea (MNU)-induced photoreceptor injury and analyzed the role of Müller glia proliferation in the regulation of their expression using retinal explant cultures. Thymidine-induced G1/S arrest of Müller glia proliferation significantly hampered the expression of Ascl1, Ngn2, and GFAP, and release from the arrest induced their upregulation. The migration of Müller glia nuclei into the outer nuclear layer was also shown to be cell cycle-dependent. These data suggest that, unlike the situation in zebrafish, cell cycle progression of Müller glia in mammals promotes both neurogenic reprogramming and reactive gliosis, which may be one of the mechanisms underlying the limited regenerative capacity of the mammalian retina.
Impact of long COVID on the heart rate variability at rest and during deep breathing maneuver
Authors: da Silva Andréa Lúcia Gonçalves , Vieira Luana dos Passos , Dias Luiza Scheffer , Prestes Cecília Vieira , Back Guilherme Dionir , Goulart Cassia da Luz , Arena Ross , Borghi-Silva Audrey , Trimer Renata
Published: December 2023

While the majority of individuals with coronavirus disease 2019 (COVID-19) recover completely, a significant percentage experience persistent symptom, which has been characterized as Long COVID and may be associated with cardiac and autonomic dysfunction. We evaluated heart rate variability (HRV) at rest and during deep-breathing (M-RSA) in patients with Long COVID. Case–control design involved 21 patients with Long COVID and 20 controls; the HRV was evaluated (POLAR system) at rest in the supine position and during M-RSA and expressed in time domain and non-linear analysis. In the supine position we found a reduction HRV measures in Long COVID’ patients compared to controls for: Mean_iRR (p < 0.001), STD_iRR (p < 0.001); STD_HR (p < 0.001); SD1 (p < 0.001); SD2 (p < 0.001); alpha2 (p < 0.001). In the M-RSA we found reduction Mean_iRR (p < 0.001), STD_iRR (p < 0.001), STD_HR (p < 0.001), rMSSD (p < 0.001), RR_tri-index (p < 0.001) in Long COVID’ patients except for highest Mean_HR p < 0.001. In conclusion, Long COVID reduced HRV at rest and during deep breathing. These findings may imply impairment of cardiac autonomic control when symptoms of COVID-19 persist following initial recovery.
Generation of adult hippocampal neural stem cells occurs in the early postnatal dentate gyrus and depends on cyclin D2
Authors: Pastor-Alonso Oier , Syeda Zahra Anum , Kaske Bente , García-Moreno Fernando , Tetzlaff Felix , Bockelmann Enno , Grunwald Vanessa , Martín-Suárez Soraya , Riecken Kristoffer , Witte Otto Wilhelm , Encinas Juan Manuel , Urbach Anja
Published: December 2023

Lifelong hippocampal neurogenesis is maintained by a pool of multipotent adult neural stem cells (aNSCs) residing in the subgranular zone of the dentate gyrus (DG). The mechanisms guiding transition of NSCs from the developmental to the adult state remain unclear. We show here, by using nestin-based reporter mice deficient for cyclin D2, that the aNSC pool is established through cyclin D2-dependent proliferation during the first two weeks of life. The absence of cyclin D2 does not affect normal development of the dentate gyrus until birth but prevents postnatal formation of radial glia-like aNSCs. Furthermore, retroviral fate mapping reveals that aNSCs are born on-site from precursors located in the dentate gyrus shortly after birth. Taken together, our data identify the critical time window and the spatial location of the precursor divisions that generate the persistent population of aNSCs and demonstrate the central role of cyclin D2 in this process.
Hotspot propensity across mutational processes
Authors: Arnedo-Pac Claudia , Muiños Ferran , Gonzalez-Perez Abel , Lopez-Bigas Nuria
Published: December 2023

The sparsity of mutations observed across tumours hinders our ability to study mutation rate variability at nucleotide resolution. To circumvent this, here we investigated the propensity of mutational processes to form mutational hotspots as a readout of their mutation rate variability at single base resolution. Mutational signatures 1 and 17 have the highest hotspot propensity (5–78 times higher than other processes). After accounting for trinucleotide mutational probabilities, sequence composition and mutational heterogeneity at 10 Kbp, most (94–95%) signature 17 hotspots remain unexplained, suggesting a significant role of local genomic features. For signature 1, the inclusion of genome-wide distribution of methylated CpG sites into models can explain most (80–100%) of the hotspot propensity. There is an increased hotspot propensity of signature 1 in normal tissues and de novo germline mutations. We demonstrate that hotspot propensity is a useful readout to assess the accuracy of mutation rate models at nucleotide resolution. This new approach and the findings derived from it open up new avenues for a range of somatic and germline studies investigating and modelling mutagenesis.
Ultrafast Nanoscale Imaging with High Harmonic Sources
Authors: Rothhardt J. , Loetgering L.
Published: December 2023

The principle of high harmonic generation (HHG) is the basis of a new era of compact, high-flux radiation sources, which deliver short wavelengths at ultrafast timescales. Various metrology techniques reported so far, such as pump–probe spectroscopy and microscopy, are either time-, frequency-, or space-resolved, but relatively few combined approaches exist. Recent advances in both source and algorithm development have enabled multimodal acquisition and data analysis schemes that bridge the gap between these separate domains. Here, we describe emerging techniques in ultrafast lensless imaging, which have gained traction in the HHG community. In particular, this chapter includes a discussion on coherent diffraction imaging (CDI), Fourier transform holography (FTH), and ptychography. Emphasis is given to extending the abovementioned diffractive imaging techniques to broadband experimental conditions – a necessary requirement for imaging at attosecond timescales.
Photoelectron Diffraction
Authors: Jahnke T. , Rolles D.
Published: December 2023

Scattering and diffraction of electrons and X-rays have been employed as a tool for determining structural properties of matter for many decades. In the realm of single molecules in the gas phase, the idea to use the photoelectric effect to emit an electron wave that illuminates the molecule from within emerged from pioneering theoretical work by Dehmer and Dill on molecular photoionization in the late 1970s. However, it was not until the early nineties that “Molecular-Frame Photoelectron Angular Distributions” (MFPADs) of gas-phase molecules became experimentally accessible. This chapter introduces the basic concepts of intra-molecular electron scattering, photoelectron diffraction, and photoelectron angular emission distributions. A short summary of experimental approaches used to study MFPADs is presented together with several examples that trace the development of the field, from its first results to recent time-resolved photoelectron diffraction studies with X-ray free-electron lasers.
Imaging Ultrafast Structural Dynamics with Megaelectronvolt Ultrafast Electron Diffraction
Authors: Lin M.-F. , Reid A. H. , Shen X. , Wolf T. J. A.
Published: December 2023

The use of relativistic electron pulses at kinetic energies in the megaelectronvolt (MeV) range has revolutionized investigations of ultrafast structural dynamics in recent years. This chapter reviews the technical developments leading to their application in ultrafast electron diffraction (UED) experiments. It also examines the specific properties of MeV electrons that make them ideal for such studies. We describe the instrumentation and methodology for MeV-UED in the gas phase, liquid phase, and solid state. We use the UED user facility at the SLAC National Accelerator Laboratory as an example to highlight recent experimental results from these research areas.
RF Cavity-based Ultrafast Transmission Electron Microscopy
Authors: Borrelli S. , Kempers S. T. , Mutsaers P. H. A. , Luiten O. J.
Published: December 2023

Ultrafast electron microscopy is among the most significant inventions of the 21st century, enabling an understanding of structural dynamics on atomic spatial and temporal scales. With this perspective in mind, the chapter first provides an overview of the state-of-the-art ultrafast electron microscopy field. Afterwards, the development of the first RF cavity-based ultrafast transmission electron microscope at the Eindhoven University of Technology is discussed. This device provides ∼100 femtosecond temporal resolution and an extremely high repetition rate (3 GHz or 75 MHz) while preserving the atomic spatial resolution and the high electron beam quality of a conventional transmission electron microscope, and avoiding the need for a powerful photoemission laser. The chapter presents the working principle and design of the Eindhoven ultrafast microscope along with the unique applications that have emerged from this method, ranging from high-repetition-rate pump–probe experiments and radiation damage suppression to coherent manipulation of electron pulses with light.
AccuTOF-DART for Rapid Presumptive Screening of Drugs of Abuse
Authors: Bennett Mark , Musselman Brian
Published: December 2023

Methods described in this chapter enable rapid and confident drug identification in the forensic laboratory. The use of direct analysis in real time ionization with high-resolution time-of-flight mass spectrometry to generate accurate mass and fragment ions is described with examples covering the detection of both major and minor compounds present in samples. The development of publicly available drug libraries and spectrum search technology is also reported to complete this chapter.
Time-resolved spectroscopy applied to heterogeneous photocatalytic materials (2019–2022)
Authors: Spies Laura , Schneider Jenny , Curti Mariano
Published: December 2023

While heterogeneous photocatalysis holds great promise for solar energy conversion, increasing photocatalytic efficiency remains a challenge due to the complexity of underlying mechanisms. Time-resolved spectroscopic techniques provide valuable insights into photocatalytic processes. This chapter reviews recent applications of these techniques to both well-established photocatalysts and to emerging energy materials, including hybrid perovskites and covalent organic frameworks. We describe applications of transient absorption spectroscopy and time-resolved terahertz spectroscopy to reveal intermediates, charge carrier transfer and recombination dynamics, and photophysical processes. Moreover, we provide an overview of the emerging technique of two-dimensional electronic spectroscopy, which has recently offered unprecedented insights into ultrafast dynamics and quantum coherent phenomena in photocatalytic materials. This chapter thus intends to inspire researchers on how time-resolved spectroscopies could help understand the underlying mechanisms, which will be the key to achieving sustainable sunlight conversion technologies based on photocatalysis.
Photophysics of transition metal complexes (2021–2022)
Authors: La Cognata Sonia , Vadivel Dhanalakshmi , Poggi Antonio , Dondi Daniele , Amendola Valeria
Published: December 2023

This Chapter summarizes the major advances in the photophysics of transition metal complexes, achieved in 2021 and 2022, covering mainly d-block metal complexes. The applications proposed span from photocatalysis and solar energy conversion to optoelectronics and bioimaging or photodynamic therapy. The previously observed trend to replace coinage metals, such as Pt, Ru and Re, with Earth-abundant first row transition elements has been confirmed.
Photochemical routes to artemisinin
Authors: Lancel M. , Tambosco B. , Amara Z.
Published: December 2023

Since its discovery in 1971, artemisinin has been and continues to be at the forefront of the fight against malaria. The commercial importance of this compound has fuelled historical breakthrough innovations over the past decades. Among them, synthetic biology and photochemistry have been two transformative technologies. The focus of this book chapter is to highlight the tremendous developments which have been made in the field of photochemistry in the artemisinin context. This summarizes the early investigations on the biosynthesis and total synthesis of artemisinin involving photochemistry as a key step, which have led to the foundation of today’s large scale photochemical process developed and operated by Sanofi in 2013. However, market competition has led to further investments and developments, in particular using continuous flow photochemical reactors and more recently, in the development of new recyclable and bifunctional photocatalytic systems as well as new routes which have become increasingly cost-efficient and sustainable.
Advances in polaritonic photochemistry
Authors: Fregoni Jacopo
Published: December 2023

When confined light interacts strongly with molecular electronic transitions, the states of the system become hybrid between light and molecules: polaritons. Resorting to molecular polaritons is a valuable strategy to manipulate the energy levels of molecules and the reaction pathways in photochemical reactions. In this review, we first adapt the conceptual tools of traditional photochemistry to the case of polaritons, highlighting the main analogies and differences with respect to purely electronic transitions. We then make use of such tools to understand the basic idea of a series of selected and promising applications aimed at manipulating photochemical processes with quantum light.
New synthetic strategies based on photoinduced halogen-atom transfer (XAT)
Authors: Juliá Fabio
Published: December 2023

The generation of carbon radicals from alkyl and aryl halides via halogen-atom transfer (XAT) represents an effective tool to access versatile intermediates for organic synthesis. Although the field has been classically dominated by methods relying on the use of hazardous reagents under thermal conditions, the development of new photochemical conditions to promote XAT reactions has represented a breakthrough in the field, enabling unprecedented transformations featuring high chemoselectivity under mild conditions. Here is described a compilation of general aspects and guidelines to understand this type of reactivity, as well as an overview of relevant recent advances on new synthetic strategies based on photoinduced XAT.
Metal-based chromophores for photochemical water oxidation
Authors: Ielo I. , Cancelliere A. M. , Arrigo A. , La Ganga G.
Published: December 2023

The energy emergency is a severe criticality for the continuous growth of the world population. In this context, there are multiple demands to produce sustainable and carbon-neutral energy capable of meeting the needs of future generations, such as the production of systems for artificial photosynthesis (AP). Photosensitizers (PS) play a crucial role in light absorption and charge separation for AP materials, when suitably-designed for obtaining excellent tunability and performance. This review discusses the studies of the last 10 years on the synthesis of efficient and performing chromophores based on metal complexes for the photo-oxidation of water. In particular, photosensitizers in homogeneous and heterogeneous phase catalytic systems are discussed, whose design aimed to improve the understanding of the photo-oxidative mechanisms and promote higher efficiency and stability of photosynthetic systems. Recent advances in dyad and multicomponent systems both in homogeneous phases and when incorporated into polymeric matrices for heterogeneous catalysis are reviewed. Finally, the significant progress in developing highly performing photoanodes are discussed. Indeed, by varying the distance of the PS from the semiconductor surface and the distance from the catalyst (C), it was possible to study different methods and molecular approaches in the construction of photoanodes for dye-sensitized photoelectrosynthetic cells (DSPEC).
Photocatalytic enantioselective radical transformation enabled by radical–polar crossover
Authors: Zhu Yue-Die , Wang Pu-Sheng
Published: December 2023

Asymmetric transformation of radicals has always been recognized as a highly challenging issue, compared with the well-developed enantioinduction methods in traditional polar/ionic chemistry. Enantioselective radical polar crossover (RPC) reactions have recently emerged as valuable and powerful tools to assemble molecular complexity that would be impossible using either a radical or polar approach alone. This chapter summarizes the recent and synthetically important stereoselective RPC transformations by merging photoredox catalysis.
Nanocomposite-based Green Supercapacitors: Advantages and Limitations
Authors: Choudhary R. B. , Ansari S.
Published: December 2023

The concept of green energy technology is necessary for a safe, sound, and healthy society. Within the strategic framework of green energy storage technology, supercapacitors stand out as a highly efficient and renewable candidate. They are reversible and rechargeable, and have less environmental impact. Energy professionals are striving to design biobased supercapacitors using porous carbon materials. Others are exploring the possibilities for fabricating high performance supercapacitor materials derived from biowastes, forest flowers, nonedible seeds, leaves, and stems. These manifest dual advantages such as fabrication of green supercapacitor precursors and reducing excessive biowastes. Nonetheless, they also possess numerous commendable characteristics, including high porosities, relatively low costs, and ease of accessibility. Adversely, they suffer from low energy density, inferior cyclic stability and poor specific capacitance. These limitations can be resolved by employing innovative techniques including tuning of surface morphology, doping with chemically attuned nanofillers, and fabrication of nanocomposites. In this chapter, detailed advantages and possible limitations of nanocomposite-based green supercapacitor materials for green and efficacious energy storage devices are described.
Applications of Green Supercapacitors in Transportation Systems
Authors: Kosnan M. A. , Azam M. A. , Takasaki A.
Published: December 2023

Emerging technology-based market economic growth has resulted in the rapid urbanization and the expansion of existing major cities. Due to this, large cities in rising economies are experiencing traffic congestion and thus worsening air quality. One approach to these issues is to develop a comprehensive transportation system based on sustainable energy sources. Green supercapacitors and other novel electric energy generation/storage devices could greatly improve the ecological situation in such densely populated cities. However, to realize this, supercapacitors must be mass-produced using clean, green technology, and environmentally benign materials, particularly from abundant, sustainable resources such as agricultural waste generated by other technological cycles. As time passes, research advances toward giving a cheaper, more sustainable alternative to present models, which may be the game changer for existing supercapacitor technology for transportation systems. Researchers throughout the world emphasize the need for lowering the cost of electrode manufacturing and the dependency on essential materials as a significant part in decarbonizing the transportation industry alongside batteries and fuel cells.
Sustainability of Green Nanocomposite-based Supercapacitors: Advances and Limitations
Authors: Kumar Tanuj , Verma Arunima , Vandana
Published: December 2023

The growing environmental and sustainability awareness has encouraged efforts to design nanobased composite materials for various end-use applications and as a unique alternative to nonrenewable synthetic fibers, such as glass and carbon-reinforced nanocomposites. Supercapacitors, on the other hand, play a key role in energy storage and conversion systems. With increased scientific activity and publications on this subject over the previous decade, researchers have created improved techniques to enhance electrode materials. Many other materials have been proposed and researched, but carbonaceous materials remain the most promising for use in supercapacitors. To overcome the limitations of individual materials, particularly while considering the density and longevity of energy, nanocomposite materials have been widely employed. The majority of them are composites of carbon-based nanoparticles and other components. We describe current achievements in the area of nanocomposite materials, including green nanocomposite-based supercapacitors, in this chapter. We concentrate on scenarios in which a single material has a disadvantage that may be solved by the process of mixing it with other green nanocomponents, allowing the construction of a composite material with improved performance. In this chapter, we discuss the fundamentals of nanocomposite green materials, including their production, characterization, and performance.
Fire and Explosions Investigation
Authors: Horrocks A. J. , Pitts K. , Detata D. , Dunsmore R.
Published: December 2023

The use of chemometric methods in the analysis process of fire and explosive evidence allows for enhanced detection and classification of target analytes to be achieved. There is a vast amount of research into the application of chemometrics in the analysis of ignitable liquid and explosive residues throughout forensic fire and explosion investigations. This chapter provides an overview of research that focuses on discrimination and classification, as well as the use of experimental design to optimise sampling, storage, and analysis protocols for ignitable liquid and explosive residues. The research discussed demonstrates the usefulness of chemometrics as a tool for the efficient detection and classification of forensic evidence. Further research in this area is needed so that chemometrics may be used for future method development and identification and classification of ignitable liquid and explosive residues in real-life criminal casework.