bluuebunny/crossref_metadata_2025 huggingface dataset:
Strong Dynamics in Tidal Marsh DOC Export in Response to Natural Cycles and Episodic Events From Continuous Monitoring
Authors: Menendez Alana , Tzortziou Maria , Neale Patrick , Megonigal Patrick , Powers Leanne , Schmitt‐Kopplin Philippe , Gonsior Michael
Published: June 2022

The role of tidal wetlands as hotspots for carbon and nutrient exchange with adjacent waters has been well documented, but large uncertainties remain regarding the physical and biogeochemical controls on these fluxes, which have significant implications for coastal carbon cycling and budgets. This study elucidates the variability in lateral wetland dissolved organic (DOC) fluxes tidally, seasonally, and during extreme weather events for a brackish wetland within a sub‐estuary of the northwestern Chesapeake Bay, USA. Continuous fluxes from the wetland‐draining tidal creek were calculated based on DOC concentrations ([DOC]) estimated using optical and physicochemical properties measured in situ with concurrent water flow data. Mean export was found to be 8.59 (±1.20) kg C (n = 1,128) tidal cycle−1 and annual flux from the wetland to sub‐estuary was 200.66 (±28.09) g C m−2 yr−1. Peaks in DOC flux were associated with Hurricane Joaquin in 2015, where just two tidal cycles accounted for ∼5% of annual export. Analysis of tidal creek water quality measurements reveal seasonal and tidal dependencies. Highest [DOC] and largest low versus high tide differences were observed in summer, corresponding to more fresh plant biomass and its mobilization, consistent with results from Fourier transform ion cyclotron resonance mass spectrometry. Despite summer highs in tidal creek [DOC], monthly DOC fluxes were greatest in early fall due to higher water flows. The annual flux presented here is higher than fluxes previously reported for this system, highlighting the importance of continuous measurements for monitoring carbon export under a wide range of environmental conditions.
Experiencing social exclusion changes gut microbiota composition
Authors: Kim Chong-Su , Shin Go-Eun , Cheong Yunju , Shin Ji‑Hee , Shin Dong-Mi , Chun Woo Young
Published: June 2022

Gut microbiota is suggested to regulate the host’s mental health via the gut-brain axis. In this study, we investigated the relationship between the microbiome and psychological pain due to social exclusion. Adult individuals with (n = 14) and without (n = 25) social exclusion experience were assessed for the psychological status using self-reported questionnaires: Beck Anxiety Inventory (BAI), Beck Depression Inventory, and the UCLA Loneliness Scale. The gut microbiota was analyzed by 16 S rRNA gene sequencing and bioinformatics. The exclusion group had a 1.70-fold higher total BAI score and 2.16-fold higher levels of anxiety-related physical symptoms (p < 0.05). The gut microbial profiles also differed between the two groups. The exclusion group showed higher probability of having Prevotella-enriched microbiome (odds ratio, 2.29; 95% confidence interval, 1.65–2.75; p < 0.05), a significantly reduced Firmicutes/Bacteroidetes ratio, and decreased abundance of Faecalibacterium spp. (p < 0.05) which was associated with the duration and intensity of social exclusion (p < 0.05). Our results indicate that the psychological pain due to social exclusion is correlated with the gut microbiota composition, suggesting that targeting social exclusion-related microorganisms can be a new approach to solving psychological problems and related social issues.
Selective cell cycle arrest in glioblastoma cell lines by quantum molecular resonance alone or in combination with temozolomide
Authors: Catanzaro Daniela , Milani Gloria , Bozza Angela , Bernardi Martina , Chieregato Katia , Menarin Martina , Merlo Anna , Celli Paola , Belli Romina , Peroni Daniele , Pozzato Alessandro , Pozzato Gianantonio , Raneri Fabio Angelo , Volpin Lorenzo , Ruggeri Marco , Astori Giuseppe
Published: June 2022

Background

Glioblastoma is the most aggressive form of brain cancer, characterised by high proliferation rates and cell invasiveness. Despite advances in surgery and radio-chemotherapy, patients continue to have poor prognoses, with a survival rate of 14–15 months. Thus, new therapeutic strategies are needed. Non-ionising electromagnetic fields represent an emerging option given the potential advantages of safety, low toxicity and the possibility to be combined with other therapies.

Methods

Here, the anticancer activity of quantum molecular resonance (QMR) was investigated. For this purpose, three glioblastoma cell lines were tested, and the QMR effect was evaluated on cancer cell proliferation rate and aggressiveness. To clarify the QMR mechanism of action, the proteomic asset after stimulation was delineated. Mesenchymal stromal cells and astrocytes were used as healthy controls.

Results

QMR affected cancer cell proliferation, inducing a significant arrest of cell cycle progression and reducing cancer tumorigenicity. These parameters were not altered in healthy control cells. Proteomic analysis suggested that QMR acts not only on DNA replication but also on the machinery involved in the mitotic spindle assembly and chromosome segregation. Moreover, in a combined therapy assessment, QMR significantly enhanced temozolomide efficacy.

Conclusions

QMR technology appears to be a promising tool for glioblastoma treatment.
Obtaining long-term stage-specific relative survival estimates in the presence of incomplete historical stage information
Authors: Stannard Rachael , Lambert Paul C. , Andersson Therese M.-L. , Rutherford Mark J.
Published: June 2022

Background

Completeness of recording for cancer stage at diagnosis is often historically poor in cancer registries, making it challenging to provide long-term stage-specific survival estimates. Stage-specific survival differences are driven by differences in short-term prognosis, meaning estimated survival metrics using period analysis are unlikely to be sensitive to imputed historical stage data.

Methods

We used data from the Surveillance, Epidemiology, and End Results (SEER) Program for lung, colon and breast cancer. To represent missing data patterns in less complete registry data, we artificially inflated the proportion of missing stage information conditional on stage at diagnosis and calendar year of diagnosis. Period analysis was applied and missing stage at diagnosis information was imputed under four different conditions to emulate extreme imputed stage distributions.

Results

We fit a flexible parametric model for each cancer stage on the excess hazard scale and the differences in stage-specific marginal relative survival were assessed. Estimates were also obtained from non-parametric approaches for validation. There was little difference between the 10-year stage-specific marginal relative survival estimates, regardless of the assumed historical stage distribution.

Conclusions

When conducting a period analysis, multiple imputation can be used to obtain stage-specific long-term estimates of relative survival, even when the historical stage information is largely incomplete.
Recent insights into the effects of metabolism on breast cancer cell dormancy
Authors: Bartlome Sara , Berry Catherine Cecilia
Published: June 2022

Breast cancer (BC) remains the most common cancer, as well as the leading cause of cancer mortality in women worldwide [1]. Approximately 30% of patients with early-stage BC experience metastasis or a recurrent form of the disease [2]. The phenomenon of BC dormancy, where metastasised cancer cells remain in a quiescent phase at their disseminated location and for unknown reasons can become actively proliferative again, further adds to BC’s clinical burden with treatment at this secondary stage typically proving futile. An emerging avenue of research focuses on the metabolic properties of dormant BC cells (BCCs) and potential metabolic changes causing BCCs to enter/exit their quiescent state. Here we explore several studies that have uncovered changes in carbon metabolism underlying a dormant state, with conflicting studies uncovering shifts towards both glycolysis and/or oxidative phosphorylation. This review highlights that the metabolic states/shifts of dormant BCCs seem to be dependent on different BC subtypes and receptor status; however, more work needs to be done to fully map these differences. Building on the research that this review outlines could provide new personalised therapeutic possibilities for BC patients.
Talking about Risk, UncertaintieS of Testing IN Genetics (TRUSTING): development and evaluation of an educational programme for healthcare professionals about BRCA1 & BRCA2 testing
Authors: Fallowfield Lesley , Solis-Trapala Ivonne , Starkings Rachel , May Shirley , Matthews Lucy , Eccles Diana , Evans D. Gareth , Turnbull Clare , Crawford Gillian , Jenkins Valerie
Published: June 2022

Background

Mainstreaming of germline testing demands that all healthcare professionals have good communication skills, but few have genetic testing and counselling experience. We developed and evaluated educational workshops—Talking about Risk & UncertaintieS of Testing IN Genetics (TRUSTING). Contents included: presentations and exercises, an interview with a geneticist about BRCA testing, screening and prevention implications, filmed interactions between surgeons, a genetic counsellor and geneticists with a fictitious family (proband had a BRCA2 pathogenic variant with triple-negative breast cancer, her older sister—BRCA2 heterozygous, and cousin—negative for BRCA2 variant).

Methods

Twenty-one surgeons, 5 oncologists, 18 nurses and 9 genetic counsellors participated. Knowledge (18 item MCQ), communication skills (responses to 6 questions from proband and relatives) and self-confidence (discussing 9 genetic testing issues) were assessed pre- and post workshop.

Results

Knowledge scores improved significantly post workshop (mean change = 7.06; 95% confidence interval (CI) 6.37–7.74; P < 0.001), as did communication (mean change = 5.38; 95% CI 4.37–6.38; P < 0.001) and self-confidence (P < 0.001).

Discussion

Healthcare professionals’ knowledge and self-confidence when discussing the risks and uncertainties in genetics are often poor. TRUSTING workshops significantly enhanced attendees’ navigation of communication difficulties encountered and will be rolled out more widely.
Use of anti-androgenic 5α-reductase inhibitors and risk of oesophageal and gastric cancer by histological type and anatomical sub-site
Authors: Rabbani Sirus , Santoni Giola , Lagergren Jesper , Xie Shao-Hua
Published: June 2022

Background

To investigate if anti-androgenic medications 5α-reductase inhibitors (5-ARIs) decrease the risk of developing oesophageal and gastric tumours, analysed by histological type and anatomical sub-site.

Methods

A Swedish population-based cohort study between 2005 and 2018 where men using 5-ARIs were considered exposed. For each exposed participant, ten male age-matched non-users of 5-ARIs (non-exposed) were included. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, calendar year, smoking, non-steroidal anti-inflammatory drugs/aspirin use, and statins use. Further adjustments were made depending on the tumour analysed.

Results

The cohort included 191,156 users of 5-ARIs and 1,911,560 non-users. Overall, the use of 5-ARIs was not associated with any statistically significantly reduced risk of oesophageal or cardia adenocarcinoma (adjusted HR 0.92, 95% CI 0.82–1.02) or gastric non-cardia adenocarcinoma (adjusted HR 0.90, 95% CI 0.80–1.02). However, the use of 5-ARIs indicated a decreased risk of oesophageal or cardia adenocarcinoma among obese or diabetic participants (adjusted HR 0.55, 95% CI 0.39–0.80) and a reduced risk of oesophageal squamous cell carcinoma (adjusted HR 0.49, 95% CI 0.37–0.65).

Conclusion

Users of 5-ARIs may have a decreased risk of developing oesophageal or cardia adenocarcinoma among those obese or diabetic, and a decreased risk of oesophageal squamous cell carcinoma.
Steering decision making by terminology: oligometastatic versus argometastatic
Authors: Szturz Petr , Vermorken Jan B.
Published: June 2022

Allowing selected patients with few distant metastases to undergo potentially curative local ablation, the designation “oligometastatic” has become a widely popular concept in oncology. However, accumulating evidence suggests that many of these patients harbour an unrecognised microscopic disease, leading either to the continuous development of new metastases or to an overt polymetastatic state and questioning thus an indiscriminate use of potentially harmful local ablation. In this paper, reviewing data on oligometastatic disease, we advocate the importance of identifying a true oligometastatic disease, characterised by a slow speed of development, instead of relying solely on a low number of lesions as the term “oligometastatic” implies. This is particularly relevant in clinical practice, where terminology has been shown to influence decision making. To define a true oligometastatic disease in the context of its still elusive biology and interaction with the immune system, we propose using clinical criteria. As discussed further in the paper, these criteria can be classified into three categories involving a low probability of occult metastases, low tumour growth rate and low tumour burden. Such cases with slow tumour-cell shedding and slow proliferation leave a sufficiently broad window-of-opportunity to detect and treat accessible lesions, increasing thus the odds of a cure.
Ubiquitin specific peptidase 11 as a novel therapeutic target for cancer management
Authors: Liao Yihao , Zhou Diansheng , Wang Pu , Yang Mengyue , Jiang Ning
Published: June 2022

Ubiquitination is a critical biological process in post-translational modification of proteins and involves multiple signaling pathways in protein metabolism, apoptosis, DNA damage, cell-cycle progression, and cancer development. Deubiquitinase, a specific enzyme that regulates the ubiquitination process, is also thought to be closely associated with the development and progression of various cancers. In this article, we systematically review the emerging role of the deubiquitinase ubiquitin-specific peptidase 11 (USP11) in many cancer-related pathways. The results show that USP11 promotes or inhibits the progression and chemoresistance of different cancers, including colorectal, breast, ovarian, and hepatocellular carcinomas, via deubiquitinating several critical proteins of cancer-related pathways. We initially summarize the role of USP11 in different cancers and further discuss the possibility of USP11 as a therapeutic strategy.
Sialylated glycan-modulated biomimetic ion nanochannels driven by carbohydrate–carbohydrate interactions
Authors: Xiao Jie , Lu Wenqi , Zhang Yahui , Li Minmin , Li Mingyang , Xiong Yuting , Tang Mingliang , Qin Haijuan , Zhu Zhichao , Qing Guangyan
Published: June 2022

Ion channels play key roles in regulating the ion environment inside and outside the cell. Sialylated glycans (SGs) at the terminus of voltage-gated ion channels (VGICs) are abundant and directly control the switch of VGICs, while SGs on the cell surface are also closely related to virus infection, tumor growth, and metastasis. Here, we report a biomimetic ion nanochannel device that can be precisely regulated by SG. The nanochannel device is composed of a chemically etched polyethylene terephthalate film featuring conical nanochannels and a polyethyleneimine-g-malcopyranoside (abbreviated to Mal-PEI). Maltose, core-binding units in Mal-PEI, forms multiple hydrogen-bonding interactions with SG, which triggers globule-to-coil transition of the polymer chain and blocks transmembrane ion transport, resulting in a remarkable decrease in the ionic current of the nanochannel. Based on the changes in the ionic current, this device can precisely discriminate α2-3- and α2-6-linked sialyllactose, as well as SGs and neutral saccharides. Importantly, the nanochannel device can monitor the sialylation process of lactose catalyzed by α2,6-sialyltransferase in real time, showing its good potential in enzyme activity determination and in vitro enzyme identification. This work constructs an SG-modulated nanochannel with selective and smart ion-gating behavior, exhibiting unique advantages in SG responsiveness and enzymatic activity monitoring.
Three-dimensional photonic topological insulator without spin–orbit coupling
Authors: Kim Minkyung , Wang Zihao , Yang Yihao , Teo Hau Tian , Rho Junsuk , Zhang Baile
Published: June 2022

Spin–orbit coupling, a fundamental mechanism underlying topological insulators, has been introduced to construct the latter’s photonic analogs, or photonic topological insulators (PTIs). However, the intrinsic lack of electronic spin in photonic systems leads to various imperfections in emulating the behaviors of topological insulators. For example, in the recently demonstrated three-dimensional (3D) PTI, the topological surface states emerge, not on the surface of a single crystal as in a 3D topological insulator, but along an internal domain wall between two PTIs. Here, by fully abolishing spin–orbit coupling, we design and demonstrate a 3D PTI whose topological surface states are self-guided on its surface, without extra confinement by another PTI or any other cladding. The topological phase follows the original Fu’s model for the topological crystalline insulator without spin–orbit coupling. Unlike conventional linear Dirac cones, a unique quadratic dispersion of topological surface states is directly observed with microwave measurement. Our work opens routes to the topological manipulation of photons at the outer surface of photonic bandgap materials.
Bifurcation drives the evolution of assembly-line biosynthesis
Authors: Booth Thomas J. , Bozhüyük Kenan A. J. , Liston Jonathon D. , Batey Sibyl F. D. , Lacey Ernest , Wilkinson Barrie
Published: June 2022

Reprogramming biosynthetic assembly-lines is a topic of intense interest. This is unsurprising as the scaffolds of most antibiotics in current clinical use are produced by such pathways. The modular nature of assembly-lines provides a direct relationship between the sequence of enzymatic domains and the chemical structure of the product, but rational reprogramming efforts have been met with limited success. To gain greater insight into the design process, we wanted to examine how Nature creates assembly-lines and searched for biosynthetic pathways that might represent evolutionary transitions. By examining the biosynthesis of the anti-tubercular wollamides, we uncover how whole gene duplication and neofunctionalization can result in pathway bifurcation. We show that, in the case of the wollamide biosynthesis, neofunctionalization is initiated by intragenomic recombination. This pathway bifurcation leads to redundancy, providing the genetic robustness required to enable large structural changes during the evolution of antibiotic structures. Should the new product be non-functional, gene loss can restore the original genotype. However, if the new product confers an advantage, depreciation and eventual loss of the original gene creates a new linear pathway. This provides the blind watchmaker equivalent to the design, build, test cycle of synthetic biology.
A global lipid map reveals host dependency factors conserved across SARS-CoV-2 variants
Authors: Farley Scotland E. , Kyle Jennifer E. , Leier Hans C. , Bramer Lisa M. , Weinstein Jules B. , Bates Timothy A. , Lee Joon-Yong , Metz Thomas O. , Schultz Carsten , Tafesse Fikadu G.
Published: June 2022

A comprehensive understanding of host dependency factors for SARS-CoV-2 remains elusive. Here, we map alterations in host lipids following SARS-CoV-2 infection using nontargeted lipidomics. We find that SARS-CoV-2 rewires host lipid metabolism, significantly altering hundreds of lipid species to effectively establish infection. We correlate these changes with viral protein activity by transfecting human cells with each viral protein and performing lipidomics. We find that lipid droplet plasticity is a key feature of infection and that viral propagation can be blocked by small-molecule glycerolipid biosynthesis inhibitors. We find that this inhibition was effective against the main variants of concern (alpha, beta, gamma, and delta), indicating that glycerolipid biosynthesis is a conserved host dependency factor that supports this evolving virus.
Highly luminescent scintillating hetero-ligand MOF nanocrystals with engineered Stokes shift for photonic applications
Authors: Perego J. , Bezuidenhout Charl X. , Villa I. , Cova F. , Crapanzano R. , Frank I. , Pagano F. , Kratochwill N. , Auffray E. , Bracco S. , Vedda A. , Dujardin C. , Sozzani P. E. , Meinardi F. , Comotti A. , Monguzzi A.
Published: June 2022

Large Stokes shift fast emitters show a negligible reabsorption of their luminescence, a feature highly desirable for several applications such as fluorescence imaging, solar-light managing, and fabricating sensitive scintillating detectors for medical imaging and high-rate high-energy physics experiments. Here we obtain high efficiency luminescence with significant Stokes shift by exploiting fluorescent conjugated acene building blocks arranged in nanocrystals. Two ligands of equal molecular length and connectivity, yet complementary electronic properties, are co-assembled by zirconium oxy-hydroxy clusters, generating crystalline hetero-ligand metal-organic framework (MOF) nanocrystals. The diffusion of singlet excitons within the MOF and the matching of ligands absorption and emission properties enables an ultrafast activation of the low energy emission in the 100 ps time scale. The hybrid nanocrystals show a fluorescence quantum efficiency of ~60% and a Stokes shift as large as 750 meV (~6000 cm−1), which suppresses the emission reabsorption also in bulk devices. The fabricated prototypal nanocomposite fast scintillator shows benchmark performances which compete with those of some inorganic and organic commercial systems.
Electrochemically driven regioselective C−H phosphorylation of group 8 metallocenes
Authors: Zheng Hao , Liu Chang-Hui , Guo Shi-Yu , He Gu-Cheng , Min Xiang-Ting , Zhou Bo-Chao , Ji Ding-Wei , Hu Yan-Cheng , Chen Qing-An
Published: June 2022

Metallocenes are privileged backbones for synthesis and catalysis. However, the direct dehydrogenative C−H functionalization of unsymmetric metallocenes suffers from reactivity and selectivity issues. Herein, we report an electrochemically driven regioselective C−H phosphorylation of group 8 metallocenes. Mechanistic investigations indicate this dehydrogenative cross coupling occurs through an electrophilic radical substitution of the metallocene with a phosphoryl radical, facilitated by the metallocene itself. This work not only offers an efficient and divergent synthesis of phosphorylated metallocenes, but also provides a guide to interpret the reactivity and regioselectivity for the C−H functionalization of unsymmetric metallocenes.
Secondary through-space interactions facilitated single-molecule white-light emission from clusteroluminogens
Authors: Zhang Jianyu , Alam Parvej , Zhang Siwei , Shen Hanchen , Hu Lianrui , Sung Herman H. Y. , Williams Ian D. , Sun Jianwei , Lam Jacky W. Y. , Zhang Haoke , Tang Ben Zhong
Published: June 2022

Clusteroluminogens refer to some non-conjugated molecules that show visible light and unique electronic properties with through-space interactions due to the formation of aggregates. Although mature and systematic theories of molecular photophysics have been developed to study conventional conjugated chromophores, it is still challenging to endow clusteroluminogens with designed photophysical properties by manipulating through-space interactions. Herein, three clusteroluminogens with non-conjugated donor-acceptor structures and different halide substituents are designed and synthesized. These compounds show multiple emissions and even single-molecule white-light emission in the crystalline state. The intensity ratio of these emissions is easily manipulated by changing the halide atom and excitation wavelength. Experimental and theoretical results successfully disclose the electronic nature of these multiple emissions: through-space conjugation for short-wavelength fluorescence, through-space charge transfer based on secondary through-space interactions for long-wavelength fluorescence, and room-temperature phosphorescence. The introduction of secondary through-space interactions to clusteroluminogens not only enriches their varieties of photophysical properties but also inspires the establishment of novel aggregate photophysics for clusteroluminescence.
FUNDC2 promotes liver tumorigenesis by inhibiting MFN1-mediated mitochondrial fusion
Authors: Li Shuaifeng , Han Shixun , Zhang Qi , Zhu Yibing , Zhang Haitao , Wang Junli , Zhao Yang , Zhao Jianhui , Su Lin , Li Li , Zhou Dawang , Ye Cunqi , Feng Xin-Hua , Liang Tingbo , Zhao Bin
Published: June 2022

Mitochondria generate ATP and play regulatory roles in various cellular activities. Cancer cells often exhibit fragmented mitochondria. However, the underlying mechanism remains elusive. Here we report that a mitochondrial protein FUN14 domain containing 2 (FUNDC2) is transcriptionally upregulated in primary mouse liver tumors, and in approximately 40% of human hepatocellular carcinoma (HCC). Importantly, elevated FUNDC2 expression inversely correlates with patient survival, and its knockdown inhibits liver tumorigenesis in mice. Mechanistically, the amino-terminal region of FUNDC2 interacts with the GTPase domain of mitofusin 1 (MFN1), thus inhibits its activity in promoting fusion of outer mitochondrial membrane. As a result, loss of FUNDC2 leads to mitochondrial elongation, decreased mitochondrial respiration, and reprogrammed cellular metabolism. These results identified a mechanism of mitochondrial fragmentation in cancer through MFN1 inhibition by FUNDC2, and suggested FUNDC2 as a potential therapeutic target of HCC.
ZFP281-BRCA2 prevents R-loop accumulation during DNA replication
Authors: Wang Yan , Ma Binbin , Liu Xiaoxu , Gao Ge , Che Zhuanzhuan , Fan Menghan , Meng Siyan , Zhao Xiru , Sugimura Rio , Cao Hua , Zhou Zhongjun , Xie Jing , Lin Chengqi , Luo Zhuojuan
Published: June 2022

R-loops are prevalent in mammalian genomes and involved in many fundamental cellular processes. Depletion of BRCA2 leads to aberrant R-loop accumulation, contributing to genome instability. Here, we show that ZFP281 cooperates with BRCA2 in preventing R-loop accumulation to facilitate DNA replication in embryonic stem cells. ZFP281 depletion reduces PCNA levels on chromatin and impairs DNA replication. Mechanistically, we demonstrate that ZFP281 can interact with BRCA2, and that BRCA2 is enriched at G/C-rich promoters and requires both ZFP281 and PRC2 for its proper recruitment to the bivalent chromatin at the genome-wide scale. Furthermore, depletion of ZFP281 or BRCA2 leads to accumulation of R-loops over the bivalent regions, and compromises activation of the developmental genes by retinoic acid during stem cell differentiation. In summary, our results reveal that ZFP281 recruits BRCA2 to the bivalent chromatin regions to ensure proper progression of DNA replication through preventing persistent R-loops.
Onasemnogene abeparvovec for presymptomatic infants with two copies of SMN2 at risk for spinal muscular atrophy type 1: the Phase III SPR1NT trial
Authors: Strauss Kevin A. , Farrar Michelle A. , Muntoni Francesco , Saito Kayoko , Mendell Jerry R. , Servais Laurent , McMillan Hugh J. , Finkel Richard S. , Swoboda Kathryn J. , Kwon Jennifer M. , Zaidman Craig M. , Chiriboga Claudia A. , Iannaccone Susan T. , Krueger Jena M. , Parsons Julie A. , Shieh Perry B. , Kavanagh Sarah , Tauscher-Wisniewski Sitra , McGill Bryan E. , Macek Thomas A.
Published: June 2022

SPR1NT (NCT03505099) was a Phase III, multicenter, single-arm study to investigate the efficacy and safety of onasemnogene abeparvovec for presymptomatic children with biallelicSMN1mutations treated at ≤6 weeks of life. Here, we report final results for 14 children with two copies ofSMN2, expected to develop spinal muscular atrophy (SMA) type 1. Efficacy was compared with a matched Pediatric Neuromuscular Clinical Research natural-history cohort (n = 23). All 14 enrolled infants sat independently for ≥30 seconds at any visit ≤18 months (Bayley-III item #26;P < 0.001; 11 within the normal developmental window). All survived without permanent ventilation at 14 months as per protocol; 13 maintained body weight (≥3rd WHO percentile) through 18 months. No child used nutritional or respiratory support. No serious adverse events were considered related to treatment by the investigator. Onasemnogene abeparvovec was effective and well-tolerated for children expected to develop SMA type 1, highlighting the urgency for universal newborn screening.
Onasemnogene abeparvovec for presymptomatic infants with three copies of SMN2 at risk for spinal muscular atrophy: the Phase III SPR1NT trial
Authors: Strauss Kevin A. , Farrar Michelle A. , Muntoni Francesco , Saito Kayoko , Mendell Jerry R. , Servais Laurent , McMillan Hugh J. , Finkel Richard S. , Swoboda Kathryn J. , Kwon Jennifer M. , Zaidman Craig M. , Chiriboga Claudia A. , Iannaccone Susan T. , Krueger Jena M. , Parsons Julie A. , Shieh Perry B. , Kavanagh Sarah , Wigderson Melissa , Tauscher-Wisniewski Sitra , McGill Bryan E. , Macek Thomas A.
Published: June 2022

Most children with biallelicSMN1deletions and threeSMN2copies develop spinal muscular atrophy (SMA) type 2. SPR1NT (NCT03505099), a Phase III, multicenter, single-arm trial, investigated the efficacy and safety of onasemnogene abeparvovec for presymptomatic children with biallelicSMN1mutations treated within six postnatal weeks. Of 15 children with threeSMN2copies treated before symptom onset, all stood independently before 24 months (P < 0.0001; 14 within normal developmental window), and 14 walked independently (P < 0.0001; 11 within normal developmental window). All survived without permanent ventilation at 14 months; ten (67%) maintained body weight (≥3rd WHO percentile) without feeding support through 24 months; and none required nutritional or respiratory support. No serious adverse events were considered treatment-related by the investigator. Onasemnogene abeparvovec was effective and well-tolerated for presymptomatic infants at risk of SMA type 2, underscoring the urgency of early identification and intervention.
Perovskite- and Dye-Sensitized Solar-Cell Device Databases Auto-generated Using ChemDataExtractor
Authors: Beard Edward J. , Cole Jacqueline M.
Published: June 2022

The number of scientific publications reporting cutting-edge third-generation photovoltaic devices is increasing rapidly, owing to the pressing need to develop renewable-energy technologies that address the climate-change crisis. Consequently, the field could benefit from a central repository where photovoltaic-performance metrics, such as the power-conversion efficiency (η) are recorded. We present two automatically generated databases that contain photovoltaic properties and device material data for dye-sensitized solar cells (DSCs) and perovskite solar cells (PSCs), totalling 660,881 data entries representing 57,678 photovoltaic devices. The databases were generated by applying the text-mining toolkit ChemDataExtractor on a corpus of 25,720 articles. A multi-faceted evaluation, incorporating manual and automatic methods, was applied to ensure that the data contained therein were of the highest quality, with precision metrics ranging from 73.1% to 95.8%. The DSC database contains 475,045 entries representing 41,680 devices, and the PSC database contains 185,836 entries representing 15,818 devices. The databases are available in MongoDB and JSON formats, which can be queried in Python, R, Java and MATLAB for data-driven photovoltaic materials discovery.
Histone deacetylase 2 inhibitor valproic acid attenuates bisphenol A-induced liver pathology in male mice
Authors: Al-Griw Mohamed A. , Alshibani Zaynab Osama , Alghazeer Rabia , Elhensheri Mohamed , Tabagh Refaat. M. , Eskandrani Areej A. , Alansari Wafa S. , Habibulla Mahmoud M. , Shamlan Ghalia
Published: June 2022

Accumulating evidence indicates the role of endocrine disruptor bisphenol A (BPA) in many pathological conditions. Histone deacetylase (HDAC) inhibition has potential for the treatment of many diseases/abnormalities. Using a mouse BPA exposure model, this study investigated the hepatoprotective effects of the Food and Drug Administration–approved HDAC2 inhibitor valproic acid (VPA) against BPA-induced liver pathology. We randomly divided 30 adult male Swiss albino mice (8 weeks old; N = 6) into five groups: group 1, no treatment (sham control (SC)); group 2, only oral sterile corn oil (vehicle control (VC)); group 3, 4 mg/kg/day of oral BPA (single dose (BPA group)); group 4, 0.4% oral VPA (VPA group); and group 5, oral BPA + VPA (BPA + VPA group). At the age of 10 weeks, the mice were euthanized for biochemical and histological examinations. BPA promoted a significant decrease in the body weight (BW), an increase in the liver weight, and a significant increase in the levels of liver damage markers aspartate aminotransferase and alanine aminotransferase in the BPA group compared to SC, as well as pathological changes in liver tissue. We also found an increase in the rate of apoptosis among hepatocytes. In addition, BPA significantly increased the levels of oxidative stress indices, malondialdehyde, and protein carbonylation but decreased the levels of reduced glutathione (GSH) in the BPA group compared to SC. In contrast, treatment with the HDAC2 inhibitor VPA significantly attenuated liver pathology, oxidative stress, and apoptosis and also enhanced GSH levels in VPA group and BPA + VPA group. The HDAC2 inhibitor VPA protects mice against BPA-induced liver pathology, likely by inhibiting oxidative stress and enhancing the levels of antioxidant-reduced GSH.
Extra-neural signals from severed nerves enable intrinsic hand movements in transhumeral amputations
Authors: Ahkami Bahareh , Mastinu Enzo , Earley Eric J. , Ortiz-Catalan Max
Published: June 2022

Robotic prostheses controlled by myoelectric signals can restore limited but important hand function in individuals with upper limb amputation. The lack of individual finger control highlights the yet insurmountable gap to fully replacing a biological hand. Implanted electrodes around severed nerves have been used to elicit sensations perceived as arising from the missing limb, but using such extra-neural electrodes to record motor signals that allow for the decoding of phantom movements has remained elusive. Here, we showed the feasibility of using signals from non-penetrating neural electrodes to decode intrinsic hand and finger movements in individuals with above-elbow amputations. We found that information recorded with extra-neural electrodes alone was enough to decode phantom hand and individual finger movements, and as expected, the addition of myoelectric signals reduced classification errors both in offline and in real-time decoding.
Influences of social uncertainty and serotonin on gambling decisions
Authors: Bellucci Gabriele , Münte Thomas F. , Park Soyoung Q.
Published: June 2022

In many instances in life, our decisions’ outcomes hinge on someone else’s choices (i.e., under social uncertainty). Behavioral and pharmacological work has previously focused on different types of uncertainty, such as risk and ambiguity, but not so much on risk behaviors under social uncertainty. Here, in two different studies using a double-blind, placebo-controlled, within-subject design, we administrated citalopram (a selective-serotonin-reuptake inhibitor) to male participants and investigated decisions in a gambling task under social and nonsocial uncertainty. In the social condition, gamble outcomes were determined by another participant. In the nonsocial condition, gamble outcomes were determined by a coin toss. We observed increased gamble acceptance under social uncertainty, especially for gambles with lower gains and higher losses, which might be indicative of a positivity bias in social expectations in conditions of high uncertainty about others’ behaviors. A similar effect was found for citalopram, which increased overall acceptance behavior for gambles irrespective of the source of uncertainty (social/nonsocial). These results provide insights into the cognitive and neurochemical processes underlying decisions under social uncertainty, with implications for research in risk-taking behaviors in healthy and clinical populations.
Statistical determinants of visuomotor adaptation along different dimensions during naturalistic 3D reaches
Authors: Ferrea E. , Franke J. , Morel P. , Gail A.
Published: June 2022

Neurorehabilitation in patients suffering from motor deficits relies on relearning or re-adapting motor skills. Yet our understanding of motor learning is based mostly on results from one or two-dimensional experimental paradigms with highly confined movements. Since everyday movements are conducted in three-dimensional space, it is important to further our understanding about the effect that gravitational forces or perceptual anisotropy might or might not have on motor learning along all different dimensions relative to the body. Here we test how well existing concepts of motor learning generalize to movements in 3D. We ask how a subject’s variability in movement planning and sensory perception influences motor adaptation along three different body axes. To extract variability and relate it to adaptation rate, we employed a novel hierarchical two-state space model using Bayesian modeling via Hamiltonian Monte Carlo procedures. Our results show that differences in adaptation rate occur between the coronal, sagittal and horizontal planes and can be explained by the Kalman gain, i.e., a statistically optimal solution integrating planning and sensory information weighted by the inverse of their variability. This indicates that optimal integration theory for error correction holds for 3D movements and explains adaptation rate variation between movements in different planes.
Comparison of three validated systems to analyse spinal shape and motion
Authors: Dreischarf Bettina , Koch Esther , Dreischarf Marcel , Schmidt Hendrik , Pumberger Matthias , Becker Luis
Published: June 2022

The assessment of spinal shape and mobility is of great importance for long-term therapy evaluation. As frequent radiation should be avoided, especially in children, non-invasive measurements have gained increasing importance. Their comparability between each other however stays elusive. Three non-invasive measurement tools have been compared to each other: Idiag M360, raster stereography and Epionics SPINE. 30 volunteers (15 females/15 males) have each been assessed by each system, investigating lumbar lordosis, thoracic kyphosis and spinal range-of-motion in the sagittal plane. Lumbar lordosis differed significantly (p < 0.001) between measurement devices but correlated significant to each other (Pearson’s r 0.5–0.6). Regarding thoracic kyphosis no significant difference and a high correlation (r = 0.8) could be shown between Idiag M360 and raster stereography. For lumbar mobility resulting measurements differed significantly and correlated only moderate between Idiag M360 and Epionics SPINE. Although the different measurement systems are moderate to high correlated to each other, their absolute agreement is limited. This might be explained by differences in their angle definition for lordotic and kyphotic angle, their measurement placement, or their capturing of mobility (static vs. dynamic assessment). Therefore, for long-term evaluation of the back profile, inter-modal comparison of values between different non-invasive devices should be avoided.
Image resampling and discretization effect on the estimate of myocardial radiomic features from T1 and T2 mapping in hypertrophic cardiomyopathy
Authors: Marfisi Daniela , Tessa Carlo , Marzi Chiara , Del Meglio Jacopo , Linsalata Stefania , Borgheresi Rita , Lilli Alessio , Lazzarini Riccardo , Salvatori Luca , Vignali Claudio , Barucci Andrea , Mascalchi Mario , Casolo Giancarlo , Diciotti Stefano , Traino Antonio Claudio , Giannelli Marco
Published: June 2022

Radiomics is emerging as a promising and useful tool in cardiac magnetic resonance (CMR) imaging applications. Accordingly, the purpose of this study was to investigate, for the first time, the effect of image resampling/discretization and filtering on radiomic features estimation from quantitative CMR T1 and T2 mapping. Specifically, T1 and T2 maps of 26 patients with hypertrophic cardiomyopathy (HCM) were used to estimate 98 radiomic features for 7 different resampling voxel sizes (at fixed bin width), 9 different bin widths (at fixed resampling voxel size), and 7 different spatial filters (at fixed resampling voxel size/bin width). While we found a remarkable dependence of myocardial radiomic features from T1 and T2 mapping on image filters, many radiomic features showed a limited sensitivity to resampling voxel size/bin width, in terms of intraclass correlation coefficient (> 0.75) and coefficient of variation (< 30%). The estimate of most textural radiomic features showed a linear significant (p < 0.05) correlation with resampling voxel size/bin width. Overall, radiomic features from T2 maps have proven to be less sensitive to image preprocessing than those from T1 maps, especially when varying bin width. Our results might corroborate the potential of radiomics from T1/T2 mapping in HCM and hopefully in other myocardial diseases.
Neuroergonomic assessment of developmental coordination disorder
Authors: Joshi Shawn , Weedon Benjamin D. , Esser Patrick , Liu Yan-Ci , Springett Daniella N. , Meaney Andy , Inacio Mario , Delextrat Anne , Kemp Steve , Ward Tomás , Izadi Hooshang , Dawes Helen , Ayaz Hasan
Published: June 2022

Until recently, neural assessments of gross motor coordination could not reliably handle active tasks, particularly in realistic environments, and offered a narrow understanding of motor-cognition. By applying a comprehensive neuroergonomic approach using optical mobile neuroimaging, we probed the neural correlates of motor functioning in young people with Developmental Coordination Disorder (DCD), a motor-learning deficit affecting 5–6% of children with lifelong complications. Neural recordings using fNIRS were collected during active ambulatory behavioral task execution from 37 Typically Developed and 48 DCD Children who performed cognitive and physical tasks in both single and dual conditions. This is the first of its kind study targeting regions of prefrontal cortical dysfunction for identification of neuropathophysiology for DCD during realistic motor tasks and is one of the largest neuroimaging study (across all modalities) involving DCD. We demonstrated that DCD is a motor-cognitive disability, as gross motor /complex tasks revealed neuro-hemodynamic deficits and dysfunction within the right middle and superior frontal gyri of the prefrontal cortex through functional near infrared spectroscopy. Furthermore, by incorporating behavioral performance, decreased neural efficiency in these regions were revealed in children with DCD, specifically during motor tasks. Lastly, we provide a framework, evaluating disorder impact in ecologically valid contexts to identify when and for whom interventional approaches are most needed and open the door for precision therapies.
Analysis of MRI and CT-based radiomics features for personalized treatment in locally advanced rectal cancer and external validation of published radiomics models
Authors: Shahzadi Iram , Zwanenburg Alex , Lattermann Annika , Linge Annett , Baldus Christian , Peeken Jan C. , Combs Stephanie E. , Diefenhardt Markus , Rödel Claus , Kirste Simon , Grosu Anca-Ligia , Baumann Michael , Krause Mechthild , Troost Esther G. C. , Löck Steffen
Published: June 2022

Radiomics analyses commonly apply imaging features of different complexity for the prediction of the endpoint of interest. However, the prognostic value of each feature class is generally unclear. Furthermore, many radiomics models lack independent external validation that is decisive for their clinical application. Therefore, in this manuscript we present two complementary studies. In our modelling study, we developed and validated different radiomics signatures for outcome prediction after neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) based on computed tomography (CT) and T2-weighted (T2w) magnetic resonance (MR) imaging datasets of 4 independent institutions (training: 122, validation 68 patients). We compared different feature classes extracted from the gross tumour volume for the prognosis of tumour response and freedom from distant metastases (FFDM): morphological and first order (MFO) features, second order texture (SOT) features, and Laplacian of Gaussian (LoG) transformed intensity features. Analyses were performed for CT and MRI separately and combined. Model performance was assessed by the area under the curve (AUC) and the concordance index (CI) for tumour response and FFDM, respectively. Overall, intensity features of LoG transformed CT and MR imaging combined with clinical T stage (cT) showed the best performance for tumour response prediction, while SOT features showed good performance for FFDM in independent validation (AUC = 0.70, CI = 0.69). In our external validation study, we aimed to validate previously published radiomics signatures on our multicentre cohort. We identified relevant publications on comparable patient datasets through a literature search and applied the reported radiomics models to our dataset. Only one of the identified studies could be validated, indicating an overall lack of reproducibility and the need of further standardization of radiomics before clinical application.
Analysis of clinical phenotypic and genotypic spectra in 36 children patients with Epilepsy of Infancy with Migrating Focal Seizures
Authors: Yang Haiyan , Yang Xiaofan , Cai Fang , Gan Siyi , Yang Sai , Wu Liwen
Published: June 2022

Epilepsy of Infancy with Migrating Focal Seizures (EIMFS) is a rare developmental and epileptic encephalopathy (DEEs) with unknown etiology, and poor prognosis. In order to explore new genetic etiology of EIMFS and new precision medicine treatment strategies, 36 children with EIMFS were enrolled in this study. 17/36 cases had causative variants across 11 genes, including 6 novel EIMFS genes: PCDH19, ALDH7A1, DOCK6, PRRT2, ALG1 and ATP7A. 13/36 patients had ineffective seizure control, 14/36 patients had severe retardation and 6/36 patients died. Of them, the genes for ineffective seizure control, severe retardation or death include KCNT1, SCN2A, SCN1A, ALG1, ATP7A and WWOX. 17 patients had abnormal MRI, of which 8 had ineffective seizure control, 7 had severe retardation and 4 died. 13 patients had hypsarrhythmia, of which 6 had ineffective seizure control, 6 had severe retardation and 2 died. Also, 7 patients had burst suppression, of which 1 had ineffective seizure control, 3 had severe retardation and 3 died. This study is the first to report that ALDH7A1, ATP7A, DOCK6, PRRT2, ALG1, and PCDH19 mutations cause the phenotypic spectrum of EIMFS to expand the genotypic spectrum. The genes KCNT1, SCN2A, SCN1A, ALG1, ATP7A and WWOX may be associated with poor prognosis. The patients presenting with MRI abnormalities, hypsarrhythmia and burst suppression in EEG may be associated with poor prognosis.