bluuebunny/crossref_metadata_2025 huggingface dataset:
Influences of resting-state intrinsic functional brain connectivity on the antidepressant treatment response in late-life depression
Authors: Ahmed Ryan , Boyd Brian D. , Elson Damian , Albert Kimberly , Begnoche Patrick , Kang Hakmook , Landman Bennett A. , Szymkowicz Sarah M. , Andrews Patricia , Vega Jennifer , Taylor Warren D.
Published: December 2022

Background

Late-life depression (LLD) is characterized by differences in resting state functional connectivity within and between intrinsic functional networks. This study examined whether clinical improvement to antidepressant medications is associated with pre-randomization functional connectivity in intrinsic brain networks.

Methods

Participants were 95 elders aged 60 years or older with major depressive disorder. After clinical assessments and baseline MRI, participants were randomized to escitalopram or placebo with a two-to-one allocation for 8 weeks. Non-remitting participants subsequently entered an 8-week trial of open-label bupropion. The main clinical outcome was depression severity measured by MADRS. Resting state functional connectivity was measured between a priori key seeds in the default mode (DMN), cognitive control, and limbic networks.

Results

In primary analyses of blinded data, lower post-treatment MADRS score was associated with higher resting connectivity between: (a) posterior cingulate cortex (PCC) and left medial prefrontal cortex; (b) PCC and subgenual anterior cingulate cortex (ACC); (c) right medial PFC and subgenual ACC; (d) right orbitofrontal cortex and left hippocampus. Lower post-treatment MADRS was further associated with lower connectivity between: (e) the right orbitofrontal cortex and left amygdala; and (f) left dorsolateral PFC and left dorsal ACC. Secondary analyses associated mood improvement on escitalopram with anterior DMN hub connectivity. Exploratory analyses of the bupropion open-label trial associated improvement with subgenual ACC, frontal, and amygdala connectivity.

Conclusions

Response to antidepressants in LLD is related to connectivity in the DMN, cognitive control and limbic networks. Future work should focus on clinical markers of network connectivity informing prognosis.

Registration

ClinicalTrials.gov NCT02332291
The Historical Lecture: Past, Present and Future
Authors: Green Toby
Published: December 2022

The oral performance of history has been common to many societies from Herodotus and the histories of Beowulf, to the griots of West Africa. The lecture in Western history emerged from these histories of orality, with its name showing the close connection in its origins to reading, and to the lecturer's expertise in that domain. From this starting point, lectures grew to be associated with frameworks of academic authority, as well as markers of community and shared academic, religious and civic identity. From the late eighteenth century onwards, the role of the historical lecture widened to involve public education, and was also later incorporated into political contestations by anticolonial orators such as Maya Angelou, Amílcar Cabral and Fidel Castro. In the twenty-first century, the rise of transnational technology has seen the increasing atomisation of the lecture into a space of performative and disembodied information. As technologies change, in the future the knowledge and thematic being explored in historical lectures may change. What is embraced may prove to be demonstration of mastery of the commercial technology involved in a lecture's delivery, as much as the exposition related to the lecture or reading from which knowledge and academic communities historically have built.
From the past to the future: Protecting Afghanistan’s cultural heritage – progress, fears, and hopes
Authors: Blake Janet , Masoumi Sayed Ali Naqi
Published: December 2022

Afghanistan’s cultural heritage has faced extreme challenges over recent decades, experiencing the simultaneous impacts of numerous disasters such as war, the looting of museums, illegal excavations, and deliberate destruction caused by extreme ideological beliefs – the last diminishing not only Afghanistan’s but also the world’s cultural heritage. However, these incidents and experiences have also provided lessons for the protection of cultural heritage. Despite progress since 2004, the return of the Taliban and their treatment of Afghanistan’s cultural heritage during their previous regime have raised growing concerns for the country’s cultural heritage and fears of that sad history repeating itself. In this article, we examine the progress made in protecting the rights related to cultural heritage in Afghanistan since the fall of the Taliban in 2001, especially in relation to its protection and safeguarding age. To this end, it examines the basis of the current cultural heritage legislation, the identification and registration of heritage elements, the legal tools for regulating heritage, and how its protection is monitored and evaluated. Addressing the challenges that this process faced, it questions what responsibilities should be placed on the Taliban following their recent return to power.
Family resilience during the COVID-19 onset: A daily-diary inquiry into parental employment status, parent–adolescent relationships, and well-being
Authors: Wang Ming-Te , Del Toro Juan , Henry Daphne A. , Scanlon Christina L. , Schall Jacqueline D.
Published: December 2022

COVID-19 changed the landscape of employment and financial security in the USA, contributing to multi-systemic disruptions in family life. Using dyadic, daily-diary parent–adolescent data from a nationwide American sample (18,415 daily assessments; 29 days: 4/8/2020–4/21/2020 and 5/18/2020–6/1/2020;N= 635 parent–adolescent dyads), this intensive longitudinal study investigated how COVID-19-related job loss and working-from-home (WFH) arrangements influenced parents’ and children’s daily affect indirectly through family functioning (i.e., parent–adolescent conflict, inter-adult conflict, and parental warmth) and whether these links varied by family socioeconomic status (SES). Parental employment status was linked to these family relational dynamics, which were then connected to parents’ and adolescents’ daily affect. Although SES did not moderate these links, low-income families were more likely to experience job loss, parent–adolescent conflict, and inter-adult conflict and less likely to WFH than higher-income families. As inter-relations within the family are a malleable point for intervention, clinicians working with families recovering from the fiscal impact of the COVID-19 pandemic are encouraged to use approaches that strengthen family relationships, especially between adolescents and their parents. Unemployment subsidies are discussed as a means to support families struggling with job loss, and organizations are urged to consider the benefits of WFH on employee health and work-life balance.
The history of the K-suffix -ū in Shirazi
Authors: Nourzaei Maryam
Published: December 2022

This article investigates the use and frequency of what I refer to as the K-suffixes -ō/-ū/-o in the Shirazi dialects, namely, Old and Modern Shirazi. It shows that the use of K-suffixes as definiteness markers is more highly developed in Modern Shirazi than in Old Shirazi. In Old Shirazi, the K-suffix, with its original evaluative meaning, demonstrated some degree of multi-functionality. This has mostly been lost in Modern Shirazi, and the suffix is now used to express definiteness. The high frequency of use of the K-suffix appears to be independent of genre, speaker, and speech setting. Data from a corpus of written texts in Old Shirazi, mainly comprised of poems, are quantitatively analysed, along with data from a corpus of spoken Shirazi narratives and data from a questionnaire answered by ten speakers. The results show that an evaluative suffix can develop into a definiteness marker by passing through a stage of combination with deictic markers, which paves the way for extending the use of the K-suffix to include non-deictic anaphoric tracking. This article concludes that the development of definiteness marking can proceed down a pathway that is distinct from the one normally assumed for demonstrative-based definiteness marking, even if the endpoint may be similar. The detailed documentation of this process presented here is a further contribution to Iranian studies, and augments the small group of well-documented cases of a non-demonstrative origin of definiteness marking cross-linguistically.
Impact of integrated weed management practices on cotton economics and Palmer amaranth (Amaranthus palmeri) populations
Authors: Farr Rodger , Norsworthy Jason K. , Kouame K. Badou-Jeremie , Barber L. Tom , Butts Thomas R. , Roberts Trent
Published: December 2022

The threat of herbicide-resistant weed species, such as Palmer amaranth, has driven the development of robust weed management programs that rely on more than chemicals for weed control. Previous research has shown that zero-tolerance weed thresholds, cover crops, deep tillage, and diverse herbicide programs are effective strategies for controlling Palmer amaranth. Unfortunately, research investigating the integration of all four of these weed management strategies in a system is lacking. To better leverage these integrated weed management strategies in cotton production systems, a long-term study was initiated in fall 2018 near Marianna, AR, with zero tolerance, deep tillage, a cereal rye cover crop, and either a dicamba or non-dicamba in-crop herbicide program as factors. Results found that total Palmer amaranth emergence was reduced 76% as the result of deep tillage in 2019 and, in the absence of a zero-tolerance strategy, 73% in 2020. In the absence of a zero-tolerance strategy, the combination of a non–cover crop strategy and dicamba herbicide program decreased total Palmer amaranth emergence by 73%, while the combination of a cover crop strategy and dicamba herbicide program decreased total Palmer amaranth emergence by 78% compared to the combination of a cover crop and non-dicamba herbicide program. Under a zero-tolerance strategy in 2019, tillage reduced cotton yield by 12% and partial returns by US$370 ha−1. In 2020, tillage reduced cotton yield by 14% and partial returns of US$371 ha−1 under a non-zero-tolerance strategy, while a 12% yield reduction and a US$260 ha−1 decrease in partial returns were observed under a zero-tolerance strategy. In 2019, the non-dicamba program resulted in greater partial returns than the dicamba in-crop program because of greater yield and lower program costs. However, in 2020, partial returns were greater for the dicamba in-crop herbicide program owing to greater yields achieved by this program.
Protecting Poor Neighborhoods from Landslide Risk
Authors: Besl J.
Published: December 2022

As low-income, informal settlements bloom in the tropics, their risk of landslides increases. A new modeling tool incorporates urbanization factors to protect the region’s poorest neighborhoods.
A Modified Frequency Distribution Function of Wave‐Breaking‐Induced Energy Dissipation
Authors: Kim In‐Chul , Kaihatu James M.
Published: December 2022

A nonlinear frequency‐domain model and a probabilistic wave breaking model have been employed together to simulate the propagation of nearshore wave breaking and to provide estimates of related statistical quantities such as skewness and asymmetry. This combination of models requires a pre‐specification of the frequency dependence of dissipation. Prior work has suggested that a frequency‐squared weighting for the dissipation term is most appropriate via physical arguments. However, the original frequency distribution function significantly underpredicts the higher‐order moments, particularly the accuracy of asymmetry predictions is in need of further improvement. An intensity of frequency dependence for the breaking‐induced damping coefficient is introduced here to further adjust the dissipation function in order to increase the accuracy of asymmetry predictions. By correcting the frequency dependence function with a new form of frequency dependence in the breaking coefficient, the model results are in better agreement with the measurements of the spectrum and higher‐order statistics, as well as with the free surface elevation measurements. It is also seen from testing the model with three different cases that the more evident the influence of the breaking mechanism is on the wave transformation process, the more pronounced the contribution of this modification is.
Increasingly Sophisticated Climate Models Need the Out‐Of‐Sample Tests Paleoclimates Provide
Authors: Burls Natalie , Sagoo Navjit
Published: December 2022

Climate models are becoming increasingly sophisticated as climate scientists continually work to improve the realism with which the processes influencing Earth's climate are represented. One example is the treatment of cloud microphysics: as complexity is added to cloud microphysical schemes, Earth's energy budget can respond to changes in climate forcings, such as carbon dioxide or aerosols, in new ways. This increase in degrees of freedom has illuminated larger spread in climate sensitivity across the latest generation of climate models participating Coupled Model Intercomparison Project, Phase 6, with more high climate sensitivity models (Zelinka et al., 2020, https://doi.org/10.1029/2019gl085782). Whilst the historical record gives us just over a century of data to apply toward climate sensitivity constraints (e.g., Nijsse et al., 2020, https://doi.org/10.5194/esd-11-737-2020), the ocean is still taking up much of the heat trapped by anthropogenic greenhouse gas emissions and the climate system is far from equilibrium which limits our understanding how climate sensitivity might change in response to long‐term forced climate change. Here we discuss the valuable tests that paleoclimate reconstructions can provide the latest generation of climate models, as demonstrated by the recent study of Zhu et al., 2022, https://doi.org/10.1029/2021ms002776. Their study provides an example of the benefits for climate model development when climate models are confronted with simulating climates very different from today. Ideally the climate model development stage under future iterations of CMIP will involve such tests as an effort to constrain global climate sensitivity and the regional patterns of climate, such as polar amplification and subtropical aridification.
Toward New and Independent Constraints on Global Mean Sea‐Level Highstands During the Last Glaciation (Marine Isotope Stage 3, 5a, and 5c)
Authors: Pico Tamara
Published: December 2022

Estimates of ice volume over the last 120 ka, from marine isotope Stage (MIS) 5d (∼110 ka) through MIS 3 (60–26 ka) are uncertain. Weiss et al. (2022, https://doi.org/10.1029/2021PA004361) offer an innovative new constraint on past sea level using the oxygen isotopes (δ18O) of planktic (surface and thermocline dwelling) foraminifers to infer the salinity of the Sulu Sea in the Indo‐Pacific Ocean and assess flow through the Karimata Strait (Indonesia) over the last glaciation. Based on the timing of Karimata Strait flooding, the study concludes that local relative sea level in the Karimata Strait was >−8  6 m during MIS 5c (∼100 ka) and >−12  6 m during MIS 5a (∼80 ka), relative to present. For MIS 3, a maximum possible relative sea level of −16  6 m is determined. Here, these results are placed into the context of current knowledge of last glacial sea‐level change and the implications for climate forcings and feedbacks (e.g., global average surface temperature and greenhouse gases) and ice sheet growth are discussed. By tracing past ocean circulation patterns that are modulated by the depth of shallow straits such as the Karimata Strait, Weiss et al. (2022, https://doi.org/10.1029/2021PA004361) provide independent constraints on local sea level, which are essential for improving global mean sea level reconstructions on late Pleistocene glacial‐interglacial cycles.
In‐Situ Capillary Pressure and Its Interrelationships With Flow Characteristics During Steady‐State Three‐Phase Flow in Water‐Wet Berea Sandstone
Authors: Zankoor Ahmed , Khishvand Mahdi , Piri Mohammad
Published: December 2022

We present a detailed multi‐level investigation of steady‐state three‐phase flow processes in a water‐wet Berea sandstone sample. We use high‐resolution micro‐computed tomography images acquired during micro‐scale core‐flooding experiments which include successive gas injection, waterflooding, and nonspreading oil flooding steps. We develop and employ robust techniques to comprehensively characterize and probe the complex interrelationships between the pore‐scale three‐phase capillary pressures, fluid occupancy, displacement events, and the macroscopic flow behavior. The results demonstrate that the local capillary pressures involving the invading phase rise or drop in compliance with the changes in the macroscopic flow ratios. For instance, the gas‐oil capillary pressures were at their highest levels during the gas injection process (highest gas/oil fractional flow) and dropped during the subsequent processes. More importantly, the oil‐water capillary pressure is found to sharply rise during the gas injection process, implying that the gas‐displacing‐oil‐displacing‐water double displacements are the dominant double displacement mechanism during this experiment. For the waterflooding test, the local gas‐oil capillary pressures consistently decrease due to water‐displacing‐oil‐displacing‐gas double displacement events. Moreover, the results show that the variations in the gas‐liquid capillary pressures are more significant than those in the oil‐water capillary pressures. Also, the variations in all capillary pressures during gas injection are higher than in the subsequent processes. The higher variations in capillary pressure values are attributed to more localized and less uniform pore‐scale events across the medium. Finally, the capillary pressure gradients along the flow direction are incorporated in the three‐phase relative permeability measurements.
Aptamer-functionalized smart photonic hydrogels: application for the detection of thrombin in human serum
Authors: Shen Peiyan , Li Mengru , Li Ran , Han Bo , Ma Haojie , Hou Xueyan , Zhang Yuqi , Wang Ji-Jiang
Published: December 2022

Smart photonic hydrogels based on two-dimensional photonic crystals (2DPC) provide a promising sensing platform for constructing novel chemical and biological sensors due to their facile optical signal readout and highly sensitive responsivity toward target analytes. Aptamers, as recognition elements with high selectivity and affinity, are extensively used to construct a variety of sensors. Herein, we developed two partially base complementary aptamer-functionalized 2DPC hydrogels as aptasensors for the detection of thrombin (TB) in human serum. The photonic hydrogel aptasensors swelled upon exposure to TB solution, leading to an increase in the particle spacing of the 2DPCs. The particle spacing changes were acquired by simply measuring the diameters of the Debye ring diffracted by the 2DPCs without the requirement of sophisticated instruments. The aptasensor swelling resulted from the decrease in the hydrogel cross-linking density induced by the specific binding between one of the aptamers and TB and the increase in hydrogel mixing free energy induced by the introduction of TB. The particle spacing increase of the optimized aptasensor was linear over the TB concentration range of 1–500 nM, and the limit of detection was 0.64 nM. The constructed 2DPC hydrogel aptasensor was used to detect TB in human serum and achieved recoveries of 95.74–104.21% and a relative standard deviation of 2.52–6.58%, showing the practicability and accuracy of the sensor. The aptamer-actuated 2DPC hydrogel biosensor provides a new strategy for designing other target molecule-sensitive aptasensors, showing great potential for development into home kits.
Colossal barocaloric effect achieved by exploiting the amorphous high entropy of solidified polyethylene glycol
Authors: Yu Zibing , Zhou Houbo , Hu Fengxia , Liu Chang , Yuan Shuaikang , Wang Donghui , Hao Jiazheng , Gao Yihong , Wang Yangxin , Wang Bingjie , Tian Zhengying , Lin Yuan , Zhang Cheng , Yin Zhuo , Wang Jing , Chen Yunzhong , Li Yunliang , Sun Jirong , Zhao Tongyun , Shen Baogen
Published: December 2022

The barocaloric effect (BCE) has emerged as an intense research topic in regard to efficient and clean solid-state refrigeration. Materials with solid-liquid phase transitions (SL-PTs) usually show huge melting entropies but cannot work in full solid-state refrigeration. Here, we report a colossal barocaloric effect realized by exploiting high entropy inherited from huge disorder of liquid phase in amorphous polyethylene glycol (PEG), which is solidified by introducing 5 wt.% polyethylene terephthalate (PET). Transmission electron microscopy (TEM) combined with X-ray diffraction (XRD) demonstrates the amorphous nature of the high-temperature phase after fixation by PET. Although PEG loses its –OH end mobility in amorphous solid, high entropy still retains owing to the retained high degrees of freedom of its molecular chains. The remaining entropy of amorphous PEG is up to 83% of that of liquid PEG in PEG10000/PET15000, and the barocaloric entropy change reaches ΔSp ∼ 416 J·kg−1·K−1 under a low pressure of 0.1 GPa, which exceeds the performance of most other BCE materials. Infrared spectra combined with density function theory (DFT) calculations disclose conformational change from the liquid to amorphous state, which explains the origin of the large entropy retained and hence the colossal BCE of the solidified PEG. This research opens a new avenue for exploring full solid-state barocaloric materials by utilizing genetic high entropy from huge disordering of liquid phases in various materials with SL-PTs.
Allosteric rescue of catalytically impaired ATP phosphoribosyltransferase variants links protein dynamics to active-site electrostatic preorganisation
Authors: Fisher Gemma , Corbella Marina , Alphey Magnus S. , Nicholson John , Read Benjamin J. , Kamerlin Shina C. L. , da Silva Rafael G.
Published: December 2022

ATP phosphoribosyltransferase catalyses the first step of histidine biosynthesis and is controlled via a complex allosteric mechanism where the regulatory protein HisZ enhances catalysis by the catalytic protein HisGS while mediating allosteric inhibition by histidine. Activation by HisZ was proposed to position HisGS Arg56 to stabilise departure of the pyrophosphate leaving group. Here we report active-site mutants of HisGS with impaired reaction chemistry which can be allosterically restored by HisZ despite the HisZ:HisGS interface lying ~20 Å away from the active site. MD simulations indicate HisZ binding constrains the dynamics of HisGS to favour a preorganised active site where both Arg56 and Arg32 are poised to stabilise leaving-group departure in WT-HisGS. In the Arg56Ala-HisGS mutant, HisZ modulates Arg32 dynamics so that it can partially compensate for the absence of Arg56. These results illustrate how remote protein-protein interactions translate into catalytic resilience by restoring damaged electrostatic preorganisation at the active site.
Uncomputably complex renormalisation group flows
Authors: Watson James D. , Onorati Emilio , Cubitt Toby S.
Published: December 2022

Renormalisation group methods are among the most important techniques for analysing the physics of many-body systems: by iterating a renormalisation group map, which coarse-grains the description of a system and generates a flow in the parameter space, physical properties of interest can be extracted. However, recent work has shown that important physical features, such as the spectral gap and phase diagram, may be impossible to determine, even in principle. Following these insights, we construct a rigorous renormalisation group map for the original undecidable many-body system that appeared in the literature, which reveals a renormalisation group flow so complex that it cannot be predicted. We prove that each step of this map is computable, and that it converges to the correct fixed points, yet the resulting flow is uncomputable. This extreme form of unpredictability for renormalisation group flows had not been shown before and goes beyond the chaotic behaviour seen previously.
A Multifaceted benchmarking of synthetic electronic health record generation models
Authors: Yan Chao , Yan Yao , Wan Zhiyu , Zhang Ziqi , Omberg Larsson , Guinney Justin , Mooney Sean D. , Malin Bradley A.
Published: December 2022

Synthetic health data have the potential to mitigate privacy concerns in supporting biomedical research and healthcare applications. Modern approaches for data generation continue to evolve and demonstrate remarkable potential. Yet there is a lack of a systematic assessment framework to benchmark methods as they emerge and determine which methods are most appropriate for which use cases. In this work, we introduce a systematic benchmarking framework to appraise key characteristics with respect to utility and privacy metrics. We apply the framework to evaluate synthetic data generation methods for electronic health records data from two large academic medical centers with respect to several use cases. The results illustrate that there is a utility-privacy tradeoff for sharing synthetic health data and further indicate that no method is unequivocally the best on all criteria in each use case, which makes it evident why synthetic data generation methods need to be assessed in context.
An umbrella review of the evidence linking oral health and systemic noncommunicable diseases
Authors: Botelho João , Mascarenhas Paulo , Viana João , Proença Luís , Orlandi Marco , Leira Yago , Chambrone Leandro , Mendes José João , Machado Vanessa
Published: December 2022

Oral diseases are highly prevalent worldwide. Recent studies have been supporting a potential bidirectional association of oral diseases with systemic noncommunicable diseases (NCDs). Available evidence supports that people with NCDs have a greater prevalence of oral diseases particularly those with limited ability of oral self-care. Regarding the reverse relationship, the lines of evidence pointing out NCDs as putative risk factors for oral diseases have increased significantly but not with a consistent agreement. This umbrella review of meta-analyses appraises the strength and validity of the evidence for the association between oral health and systemic health (registered at PROSPERO, ID: CRD42022300740). An extensive search included systematic reviews that have provided meta-analytic estimates on the association of oral diseases with NCDs. The overall strength of evidence was found to be unfavorable and with methodological inconsistencies. Twenty-eight NCDs were strongly associated with oral diseases. Among those NCDs are five types of cancer, diabetes mellitus, cardiovascular diseases, depression, neurodegenerative conditions, rheumatic diseases, inflammatory bowel disease, gastric helicobacter pylori, obesity, and asthma. According to fail-safe number statistics, the evidence levels are unlikely to change in the future, indicating a fairly robust consistency.
Immunogenetic losses co-occurred with seahorse male pregnancy and mutation in tlx1 accompanied functional asplenia
Authors: Liu Yali , Qu Meng , Jiang Han , Schneider Ralf , Qin Geng , Luo Wei , Yu Haiyan , Zhang Bo , Wang Xin , Zhang Yanhong , Zhang Huixian , Zhang Zhixin , Wu Yongli , Zhang Yingyi , Yin Jianping , Zhang Si , Venkatesh Byrappa , Roth Olivia , Meyer Axel , Lin Qiang
Published: December 2022

In the highly derived syngnathid fishes (pipefishes, seadragons & seahorses), the evolution of sex-role reversed brooding behavior culminated in the seahorse lineage’s male pregnancy, whose males feature a specialized brood pouch into which females deposit eggs during mating. Then, eggs are intimately engulfed by a placenta-like tissue that facilitates gas and nutrient exchange. As fathers immunologically tolerate allogenic embryos, it was suggested that male pregnancy co-evolved with specific immunological adaptations. Indeed, here we show that a specific amino-acid replacement in the tlx1 transcription factor is associated with seahorses’ asplenia (loss of spleen, an organ central in the immune system), as confirmed by a CRISPR-Cas9 experiment using zebrafish. Comparative genomics across the syngnathid phylogeny revealed that the complexity of the immune system gene repertoire decreases as parental care intensity increases. The synchronous evolution of immunogenetic alterations and male pregnancy supports the notion that male pregnancy co-evolved with the immunological tolerance of the embryo.
High-throughput robust single-cell DNA methylation profiling with sciMETv2
Authors: Nichols Ruth V. , O’Connell Brendan L. , Mulqueen Ryan M. , Thomas Jerushah , Woodfin Ashley R. , Acharya Sonia , Mandel Gail , Pokholok Dmitry , Steemers Frank J. , Adey Andrew C.
Published: December 2022

DNA methylation is a key epigenetic property that drives gene regulatory programs in development and disease. Current single-cell methods that produce high quality methylomes are expensive and low throughput without the aid of extensive automation. We previously described a proof-of-principle technique that enabled high cell throughput; however, it produced only low-coverage profiles and was a difficult protocol that required custom sequencing primers and recipes and frequently produced libraries with excessive adapter contamination. Here, we describe a greatly improved version that generates high-coverage profiles (~15-fold increase) using a robust protocol that does not require custom sequencing capabilities, includes multiple stopping points, and exhibits minimal adapter contamination. We demonstrate two versions of sciMETv2 on primary human cortex, a high coverage and rapid version, identifying distinct cell types using CH methylation patterns. These datasets are able to be directly integrated with one another as well as with existing snmC-seq2 datasets with little discernible bias. Finally, we demonstrate the ability to determine cell types using CG methylation alone, which is the dominant context for DNA methylation in most cell types other than neurons and the most applicable analysis outside of brain tissue.
CO2 electroreduction to multicarbon products in strongly acidic electrolyte via synergistically modulating the local microenvironment
Authors: Ma Zesong , Yang Zhilong , Lai Wenchuan , Wang Qiyou , Qiao Yan , Tao Haolan , Lian Cheng , Liu Min , Ma Chao , Pan Anlian , Huang Hongwen
Published: December 2022

Electrochemical CO2reduction to multicarbon products faces challenges of unsatisfactory selectivity, productivity, and long-term stability. Herein, we demonstrate CO2electroreduction in strongly acidic electrolyte (pH ≤ 1) on electrochemically reduced porous Cu nanosheets by combining the confinement effect and cation effect to synergistically modulate the local microenvironment. A Faradaic efficiency of 83.7 ± 1.4% and partial current density of 0.56 ± 0.02 A cm−2, single-pass carbon efficiency of 54.4%, and stable electrolysis of 30 h in a flow cell are demonstrated for multicarbon products in a strongly acidic aqueous electrolyte consisting of sulfuric acid and KCl with pH ≤ 1. Mechanistically, the accumulated species (e.g., K+and OH−) on the Helmholtz plane account for the selectivity and activity toward multicarbon products by kinetically reducing the proton coverage and thermodynamically favoring the CO2conversion. We find that the K+cations facilitate C-C coupling through local interaction between K+and the key intermediate *OCCO.
Gradient area-selective deposition for seamless gap-filling in 3D nanostructures through surface chemical reactivity control
Authors: Nguyen Chi Thang , Cho Eun-Hyoung , Gu Bonwook , Lee Sunghee , Kim Hae-Sung , Park Jeongwoo , Yu Neung-Kyung , Shin Sangwoo , Shong Bonggeun , Lee Jeong Yub , Lee Han-Bo-Ram
Published: December 2022

The integration of bottom-up fabrication techniques and top-down methods can overcome current limits in nanofabrication. For such integration, we propose a gradient area-selective deposition using atomic layer deposition to overcome the inherent limitation of 3D nanofabrication and demonstrate the applicability of the proposed method toward large-scale production of materials. Cp(CH3)5Ti(OMe)3 is used as a molecular surface inhibitor to prevent the growth of TiO2 film in the next atomic layer deposition process. Cp(CH3)5Ti(OMe)3 adsorption was controlled gradually in a 3D nanoscale hole to achieve gradient TiO2 growth. This resulted in the formation of perfectly seamless TiO2 films with a high-aspect-ratio hole structure. The experimental results were consistent with theoretical calculations based on density functional theory, Monte Carlo simulation, and the Johnson-Mehl-Avrami-Kolmogorov model. Since the gradient area-selective deposition TiO2 film formation is based on the fundamentals of molecular chemical and physical behaviours, this approach can be applied to other material systems in atomic layer deposition.
Strategies to capitalize on cell spheroid therapeutic potential for tissue repair and disease modeling
Authors: Griffin Katherine H. , Fok Shierly W. , Kent Leach J.
Published: December 2022

Cell therapies offer a tailorable, personalized treatment for use in tissue engineering to address defects arising from trauma, inefficient wound repair, or congenital malformation. However, most cell therapies have achieved limited success to date. Typically injected in solution as monodispersed cells, transplanted cells exhibit rapid cell death or insufficient retention at the site, thereby limiting their intended effects to only a few days. Spheroids, which are dense, three-dimensional (3D) aggregates of cells, enhance the beneficial effects of cell therapies by increasing and prolonging cell–cell and cell–matrix signaling. The use of spheroids is currently under investigation for many cell types. Among cells under evaluation, spheroids formed of mesenchymal stromal cells (MSCs) are particularly promising. MSC spheroids not only exhibit increased cell survival and retained differentiation, but they also secrete a potent secretome that promotes angiogenesis, reduces inflammation, and attracts endogenous host cells to promote tissue regeneration and repair. However, the clinical translation of spheroids has lagged behind promising preclinical outcomes due to hurdles in their formation, instruction, and use that have yet to be overcome. This review will describe the current state of preclinical spheroid research and highlight two key examples of spheroid use in clinically relevant disease modeling. It will highlight techniques used to instruct the phenotype and function of spheroids, describe current limitations to their use, and offer suggestions for the effective translation of cell spheroids for therapeutic treatments.
Effects of small molecule-induced dimerization on the programmed death ligand 1 protein life cycle
Authors: Chai Ilean , Kornyeyev Dmytro , Hsieh Edward , Magombedze Gesham , Stapleton Lance , Hung Magdeleine , Kwon Hyock Joo , Stefanutti Erin , Belzile JeanPhilippe , Czerwieniec Gregg , Wang Adele Y. , Morar Mariya , Lad Latesh
Published: December 2022

The programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) checkpoint blockade is central to Immuno-Oncology based therapies, and alternatives to antibody blockers of this interaction are an active area of research due to antibody related toxicities. Recently, small molecule compounds that induce PD-L1 dimerization and occlusion of PD-1 binding site have been identified and developed for clinical trials. This mechanism invokes an oligomeric state of PD-L1 not observed in cells previously, as PD-L1 is generally believed to function as a monomer. Therefore, understanding the cellular lifecycle of the induced PD-L1 dimer is of keen interest. Our report describes a moderate but consistent increase in the PD-L1 rate of degradation observed upon protein dimerization as compared to the monomer counterpart. This subtle change, while not resolved by measuring total PD-L1 cellular levels by western blotting, triggered investigations of the overall protein distribution across various cellular compartments. We show that PD-L1 dimerization does not lead to rapid internalization of neither transfected nor endogenously expressed protein forms. Instead, evidence is presented that dimerization results in retention of PD-L1 intracellularly, which concomitantly correlates with its reduction on the cell surface. Therefore, the obtained data for the first time points to the ability of small molecules to induce dimerization of the newly synthesized PD-L1 in addition to the protein already present on the plasma membrane. Overall, this work serves to improve our understanding of this important target on a molecular level in order to guide advances in drug development.
Evaluation of drug prescribing patterns and therapeutic drug monitoring practice using electronic medical records
Authors: Lee Sangmi , Yoon Seonghae , Jang In-Jin
Published: December 2022

Therapeutic drug monitoring (TDM) is performed for drugs with narrow therapeutic indices. At Seoul National University Hospital (SNUH) and Seoul National University Bundang Hospital (SNUBH), TDM services are provided for various drugs such as antibiotics and antiepileptics. This study aimed to identify prescription patterns over time using electronic medical records and analyze their relationship with TDM practice. Data were collected from a clinical data warehouse from 2007 to 2020, and the number of patients, total number of drug administration days, serum level tests, and TDM were calculated. The ratio was calculated as the number of serum level tests or TDM to the total number of drug administration days. The study included 136,427 and 162,927 patients from SNUH and SNUBH who were prescribed 11 specified drugs. Each drug showed different prescription patterns over time, and the serum level test and TDM also changed with prescription pattern changes. Serum level test or TDM of antibiotics was frequently used compared to antiepileptics. As some drugs’ usage and test for drugs have decreased newly developed drugs are replacing old drugs. It is recommended that TDM services include these new drugs as well for an effective and safe therapy.
Canonical NF-κB signaling pathway and GRO-α/CXCR2 axis are activated in unruptured intracranial aneurysm patients
Authors: Kamińska Joanna , Tylicka Marzena , Dymicka-Piekarska Violetta , Mariak Zenon , Matowicka-Karna Joanna , Koper-Lenkiewicz Olga Martyna
Published: December 2022

Activation of the nuclear factor kappa-B (NF-κB) stimulates the production of pro-inflammatory molecules involved in the formation of intracranial aneurysms (IA). The study aimed to assess the NF-κB p65 subunit and the GRO-α chemokine and its receptor CXCR2 concentrations in unruptured intracranial aneurysm patients (UIA, n = 25) compared to individuals without vascular changes in the brain (n = 10). It was also analyzed whether tested proteins are related to the size and number of aneurysms. Cerebrospinal fluid (CSF) and serum protein levels were measured using the ELISA method. Median CSF and serum NF-κB p65 concentrations were significantly lower, while median CSF GRO-α and CXCR2 concentrations were significantly higher in UIA patients compared to the control group. CSF and serum NF-κB p65 concentrations negatively correlated with the number of aneurysms. In UIA patients the median GRO-α concentration was two-fold and CXCR2 almost four-fold higher in CSF compared to the serum value. CSF GRO-α concentration positively correlated with the size of aneurysms.Significantly decreased CSF NF-κB p65 and significantly increased CSF GRO-α and its CXCR2 receptor concentrations in UIA patients compared to the control group may altogether suggest that the canonical NF-κB signaling pathway is activated and its target pro-inflammatory genes are highly expressed in UIA patients. However, to unequivocally assess the involvement of the classical NF-κB pathway with the participation of the NF-κB p65 subunit and the GRO-α/CXCR2 axis in the formation of IA, further in vivo model studies are needed.
Differentially expressed long noncoding RNAs in RAW264.7 macrophages during Brucella infection and functional analysis on the bacterial intracellular replication
Authors: Guan Xiang , Hu Hai , Tian Minxing , Zhuang Hongxu , Ding Chan , Yu Shengqing
Published: December 2022

Long noncoding RNAs (lncRNAs) are a group of functional RNA molecules without protein-coding potential and play vital roles in majority of biological processes. To date, the expression profiles of lncRNAs and their influence on Brucella replication in RAW264.7 cells are poorly understood. In this study, we performed high-throughput transcriptome analysis to investigate the differentially expressed lncRNAs associated with Brucella abortus S2308 infection. Of these, 8, 6, 130 and 94 cellular lncRNAs were differentially expressed at 4, 8, 24 and 48 h post-infection, respectively. Moreover, 1918 protein-coding genes are predicted as potential cis target genes of differentially expressed lncRNAs by searching protein-coding genes located at upstream and downstream of lncRNA loci on the chromosome DNA of Mus musculus. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that majority of lncRNA target genes were associated with B. abortus infection. Fourteen lncRNAs from transcriptome data were selected for qRT-PCR verification, confirming 13 were differentially expressed. Animal experiments revealed three were differentially expressed in vivo by qRT-PCR analysis. Furthermore, knockdown of LNC_000428 by CRISPR/dCas9 inhibition or Locked Nucleic Acids transfection downregulated Tnfrsf8 expression at mRNA level and increased Brucella intracellular replication. Thus, we provide a novel evidence that lncRNAs induced by Brucella-infection function on Brucella intracellular replication.
Novel selectively amplified DNA sequences in the germline genome of the Japanese hagfish, Eptatretus burgeri
Authors: Nagao Kohei , Otsuzumi Tomoko , Chinone Hitomi , Sasaki Takashi , Yoshimoto Junko , Matsuda Makiko , Kubota Souichirou , Goto Yuji
Published: December 2022

In the Japanese hagfish Eptatretus burgeri, 16 chromosomes (eliminated [E]-chromosomes) have been lost in somatic cells (2n = 36), which is equivalent to approx. 21% of the genomic DNA in germ cells (2n = 52). At least seven of the 12 eliminated repetitive DNA families isolated in eight hagfish species were selectively amplified in the germline genome of this species. One of them, EEEb1 (eliminated element of E. burgeri 1) is exclusively localized on all E-chromosomes. Herein, we identified four novel eliminated repetitive DNA families (named EEEb3–6) through PCR amplification and suppressive subtractive hybridization (SSH) combined with Southern-blot hybridization. EEEb3 was mosaic for 5S rDNA and SINE elements. EEEb4 was GC-rich repeats and has one pair of direct and inverted repeats, whereas EEEb5 and EEEb6 were AT-rich repeats with one pair and two pairs of sub-repeats, respectively. Interestingly, all repeat classes except EEEb3 were transcribed in the testes, although no open reading frames (ORF) were identified. We conducted fluorescence in situ hybridization (FISH) to examine the chromosomal localizations of EEEb3–6 and EEEb2, which was previously isolated from the germline genome of E. burgeri. All sequences were only found on all EEEb1-positive E-chromosomes. Copy number estimation of the repeated elements by slot-blot hybridization revealed that (i) the EEEb1–6 family members occupied 39.9% of the total eliminated DNA, and (ii) a small number of repeats were retained in somatic cells, suggesting that there is incomplete elimination of the repeated elements. These results provide new insights into the mechanisms involved in the chromosome elimination and the evolution of E-chromosomes.
The photochemical unit, University of Western Ontario
Authors: Albini Angelo
Published: December 2022

The years of the renaissance of molecular photochemistry are the same of the contemporary mechanistic organic chemistry and the Photochemical Unit at UWO greatly contributed to both of them. This was founded by Paul de Mayo in 1974 and involved contributions by several great scientists, among whom Donald R Arnold.
Organic aspects: photochemistry of alkenes, dienes, polyenes (2020–2021)
Authors: Tsuno Takashi
Published: December 2022

This review deals with the photochemistry of the title compounds including photocatalytic modification of alkenes, dienes and polyenes through a choice of the literature published during the period January 2020 to December 2021. This chapter also covers nanotechnology and supramolecular chemistry utilizing isomerization/electrocyclization/cycloaddition reactions.
Photochemistry of aromatic compounds (2019–2020)
Authors: Mizuno Kazuhiko
Published: December 2022

This chapter includes a large selection of photochemical reactions involving aromatic compounds, including, among others, photoisomerization, photoaddition and photocycloaddition, photodimerization, intramolecular photocyclization, photosubstitution, photo-reduction and photo-oxidation, photorearrangement reactions of aromatic compounds and related photoreactions published in the 2019–2020 period.
Oxygen-containing chromophores
Authors: Galian Raquel E. , Pérez-Prieto Julia
Published: December 2022

This chapter covers the photochemistry of carbonyl compounds and their application as reagents, catalysts or promoters of metal-free photochemical transformations reported in the mid-2020 to the mid-2022 period. The carbonyl chromophore can absorb UV–visible light and thereby generate new C–C and C–heteroatom bonds and perform complex chemical transformations through different mechanisms: Hydrogen Atom Transfer (HAT), Single Electron Transfer (SET), and Triplet Energy Transfer (ET). This chapter is mostly organized according to reaction types (Norrish type I, Norrish type II, Aza-Yang reaction, Paterno–Büchi reactions, acyl radical addition, intramolecular cyclization, photoredox-mediated Giese reaction), but also by the type of bonds generated (C–C, C–heteroatom bonds) by either a photocatalytic or a non-photocatalytic reaction. Mechanistic information available by means of steady-state and time-resolved studies, as well as the information derived from theoretical calculations, or control studies are briefly commented on.
Recent advances in palladium photocatalyzed transformations (2017–2021)
Authors: Lambruschini Chiara , Basso Andrea
Published: December 2022

Visible light-induced transition metal catalysis has recently emerged as an innovative approach, where a transition metal complex plays a dual role by harvesting photon energy and enabling bond forming/breaking reactions. Unprecedented transformations, as well as the improvement of known reactions, can be achieved by this novel approach and different metals, such as palladium, nickel, copper and others, can be successfully employed. Due to the distinct excited-state reactivity of each metal and the high variety of transformations involved, this chapter focuses only on palladium and its applications, postponing the discussion on other metals in future chapters of this series.
Recent approaches in asymmetric non-covalent organo-photocatalysis
Authors: Marzo Leyre , Alemán José
Published: December 2022

In this chapter we aim to collect the main advances in asymmetric photocatalysis mediated by non-covalent organocatalysis. In the first part, we will discuss approaches in which the chiral catalyst interacts with the substrate in the excited state, whereas in the second section we will review processes where the stereoinduction takes place in the ground state.
Recent advances of visible-light-induced carbon–sulfur bond formation
Authors: Feng Jiaxu , Lu Kui , Zhao Xia
Published: December 2022

Sulfur-based functional groups are widely diffuse in several natural products, bioactive molecules, and organic functional materials. The most recent advances on photochemical and photocatalyzed protocols for the formation of carbon–sulfur bond are covered in the present chapter.