bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurodevelopmental Disorders in Offspring Conceived via In Vitro Fertilization vs Intracytoplasmic Sperm Injection
Authors: Lo Huiwen , Weng Shih-Feng , Tsai Eing-Mei 
Published: December 2022

ImportanceIntracytoplasmic sperm injection (ICSI), the most common type of assisted reproductive technology (ART), might damage the sperm or embryo. The implications of male infertility and ICSI for the neurodevelopmental health of offspring remain unknown.ObjectiveTo analyze the risks of neurodevelopmental disorders in offspring of couples with male or female infertility with or without ICSI use.Design, Setting, and ParticipantsThis cohort study was conducted in Taiwan and used information collected from the national population registry data set, national birth data set, and national ART data set for all live singleton births from January 1, 2008, to December 31, 2016. The follow-up period started from the date of birth until the diagnosis of a disorder or December 31, 2018, whichever occurred first. Data were analyzed from July 1, 2021, to August 1, 2022.ExposuresMale or female infertility with or without ICSI.Main Outcomes and MeasuresThe outcome was the incidence of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and developmental delay in offspring with ART conception. Taiwan’s national population registry data set was used to identify ASD, ADHD, and developmental delay diagnosed in outpatient clinic and hospitalization records.ResultsThe study included 1 575 971 singleton births (mean [SD] age, 5.87 [2.60] years; 819 389 boys [52.0%]), of whom 1 568 257 (99.5%) had natural conception, 2111 (0.1%) had ART conception with male infertility, and 5603 (0.4%) had ART conception with female infertility. The risks of ASD (adjusted hazard ratio, 2.49; 95% CI, 1.61-3.84; P &amp;lt; .001) and developmental delay (adjusted hazard ratio, 1.92; 95% CI, 1.54-2.39; P &amp;lt; .001) in offspring with ART conception and ICSI use were significantly higher than those in offspring with natural conception. The same results were found in offspring of couples with either male or female infertility and ICSI intervention.Conclusions and RelevanceResults of this study suggest that male infertility was not associated with an increased risk of neurodevelopmental disorders in offspring. In both male and female infertility groups, ICSI had unfavorable implications for the neurodevelopmental health of offspring in terms of increased risks of ASD and developmental delay.
Survival After Minimally Invasive vs Open Surgery for Pancreatic Adenocarcinoma
Authors: Topal Halit , Aerts Raymond , Laenen Annouschka , Collignon André , Jaekers Joris , Geers Joachim , Topal Baki 
Published: December 2022

ImportanceOnly a few high-volume centers have reported on long-term oncologic outcomes after minimally invasive pancreatic surgery (MIPS) for pancreatic adenocarcinoma, but none of them have shown superior long-term overall survival (OS) compared with open pancreatic surgery (OPS).ObjectiveTo study long-term survival after MIPS and OPS with curative intent among patients with pancreatic adenocarcinoma.Design, Setting, and ParticipantsThis comparative effectiveness study used a retrospective analysis of a prospectively maintained electronic database of patient data collected between January 2010 and December 2019. Consecutive patients from a high-volume pancreatic cancer referral center were included. Data analysis was conducted from March to October 2022. Median follow-up time was 56.8 months.ExposuresPatients were matched using propensity score models to study long-term survival.Main Outcomes and MeasuresSurvival outcomes were analyzed using the Cox proportional hazards model. Variables used for propensity score correction were TNM stage, tumor dimension, lymph node status, type of operation, simultaneous vascular resection, neoadjuvant chemotherapy, adjuvant chemotherapy, sex, age, and American Society of Anesthesiologists score. Additional corrections were made for year of surgery and type of adjuvant chemotherapy.ResultsAfter propensity score matching the sample of 396 patients, there were 198 patients in the MIPS group (89 [44.9%] men; median [range] age, 68 [32-87] years) and 198 in the OPS group (94 [47.5%] men; median [range] age, 67 [39-84] years). Median OS in the MIPS group was 30.7 (95% CI, 26.2-36.8) months compared with 20.3 (95% CI, 17.6-23.5) months after OPS (hazard ratio [HR], 0.70; 95% CI, 0.56-0.87; P = .002). Median disease-free survival (DFS) after MIPS vs OPS was 14.8 (95% CI, 11.8-17.0) months vs 10.7 (95% CI, 9.0-12.1) months (HR, 0.71; 95% CI, 0.57-0.89; P = .003). Additional corrections for year of surgery and type of adjuvant chemotherapy showed better OS (year of surgery: HR, 0.74; 95% CI, 0.57-0.96; P = .02; adjuvant chemotherapy: HR, 0.71; 95% CI, 0.56-0.90; P = .005) and DFS (year of surgery: HR, 0.77; 95% CI, 0.59-0.99; P = .04; adjuvant chemotherapy: HR, 0.72; 95% CI, 0.57-0.92; P = .009) for patients undergoing minimally invasive vs open surgery.Conclusions and RelevanceIn this study of 396 patients with borderline resectable and resectable pancreatic adenocarcinoma, MIPS was associated with better OS and DFS than OPS. Centralization of MIPS should be stimulated, and pancreatic surgeons should be encouraged to pass the learning curve before implementing MIPS for pancreatic adenocarcinoma in daily clinical practice.
Efficacy of l‐Arginine treatment in patients with HTLV‐1‐associated neurological disease
Authors: Nozuma Satoshi , Matsuura Eiji , Tashiro Yuichi , Nagata Ryusei , Ando Masahiro , Hiramatsu Yu , Higuchi Yujiro , Sakiyama Yusuke , Hashiguchi Akihiro , Michizono Kumiko , Higashi Keiko , Matsuzaki Toshio , Kodama Daisuke , Tanaka Masakazu , Yamano Yoshihisa , Moritoyo Takashi , Kubota Ryuji , Takashima Hiroshi 
Published: December 2022

AbstractObjectiveHTLV‐1 infection causes HTLV‐1‐associated myelopathy/tropical spastic paraparesis (HAM/TSP), resulting in loss of motor function. In this Phase 2 trial, we assessed the efficacy and safety of l‐arginine in patients with HAM/TSP.MethodsThis open‐label, single‐arm, Phase 2 study enrolled patients diagnosed with HAM/TSP. Patients received l‐arginine at a dose of 20 g orally for 1 week and were followed‐up for 3 weeks. The primary endpoint was change in walking speed in the 10‐m walk test (10MWT). The main secondary endpoints were change in Timed Up and Go Test (TUGT) time, improvement in inflammatory markers in cerebrospinal fluid (CSF), safety, and tolerability.ResultsThe study enrolled 20 patients (13 [65%] female) with a mean age of 67.8 years (95% CI 62.3 to 73.3). Although the primary endpoint, the changes in 10MWT time between baseline (Day 0) and Day 7, did not reach statistical significance (mean percent change in time −3.5%, 95% CI −10.8% to 3.7%; P = 0.32), a significant improvement was detected between baseline and Day 14 (−9.4%, 95% CI −16.6% to −2.2%; P = 0.01). Significant improvements were also observed in selected secondary endpoints, including in TUGT time (−9.1%, 95% CI −15.5% to −2.7%; P < 0.01), and in neopterin concentration in CSF (−2.1 pmol/mL, 95% CI −3.8 to −0.5; P = 0.01). Adverse events were infrequent, mild, and resolved rapidly.Interpretationl‐arginine therapy improved motor function and decreased CSF inflammatory markers. l‐arginine thus represents a promising therapeutic option for patients with HAM/TSP.Trial Registration NumberUMIN000023854.
Grafting of Lithiophilic and Electron‐Blocking Interlayer for Garnet‐Based Solid‐State Li Metal Batteries via One‐Step Anhydrous Poly‐Phosphoric Acid Post‐Treatment
Authors: Guo Chang , Shen Yu , Mao Peng , Liao Kaiming , Du Mingjie , Ran Ran , Zhou Wei , Shao Zongping 
Published: December 2022

AbstractGarnet‐based solid‐state Li‐metal batteries (GSSBs) have the merits of high energy density and high safety. However, the realization of a stable and well‐matched Li|garnet interface for GSSBs remains challenging due to electron leakage and lithiophobic Li2CO3 impurity. To address these issues, herein, new surface chemistry is reported that converts the undesired Li2CO3 contaminant into an ultra‐thin lithium polyphosphate (Li‐PPA) layer through anhydrous polyphosphoric acid ‐induced in situ substitution reaction without damaging the water‐sensitive garnet electrolyte. In particular, the Li‐PPA interlayer not only facilitates the homogenous spreading of molten Li but also creates a robust electron‐blocking shield to suppress Li dendrite formation. As a result, the assembled Li symmetric cell exhibits a low interfacial impedance (4 Ω cm2) and high critical current density (1.8 mA cm−2) at 25 °C, which enables the cell to continuously cycle over 2500 h at 0.2 mA cm−2. Furthermore, the GSSBs paired with LiFePO4 deliver a high capacity of 149.3 mAh g−1 at 1 C and maintain 92.3% of the initial capacity after 500 cycles and can be used for solar energy storage, suggesting the feasibility of this interfacial engineering strategy for GSSBs.
Synthesis of N‐Sulfonyl Amidines and 1,3,4‐Oxadiazoles through Electrochemical Activation of DMF
Authors: Mahanty Kingshuk , Halder Atreyee , De Sarkar Suman 
Published: December 2022

AbstractElectrochemical routes for the synthesis of N‐sulfonyl amidines and 1,3,4‐oxadiazoles are reported through the activation of DMF molecule. Successful implementation of electro‐redox on dehydrative coupling and oxidative cyclization reactions eliminates the necessity of stoichiometric chemical oxidants and minimizes the generation of reagent waste. Both protocols exhibited broad functional group tolerance, permitting a widespread substrate scope with 47–94% isolated yield. Several control experiments and cyclic voltammetry studies were performed and mechanistic details of these transformations are thoroughly outlined.magnified image
Convergent Approaches and Biological Activity of C1 and/or C3 Mono or Diamino Derivatives of 1α,25‐Dihydroxy‐19‐nor‐vitamin D3. Key Enzymatic Desymmetrization of A‐Ring Synthon Precursor
Authors: González‐García Tania , Verstuyf Annemieke , Verlinden Lieve , Fernández Susana , Ferrero Miguel 
Published: December 2022

AbstractThree novel 19‐nor‐1α,25‐dihydroxyvitamin D3 derivatives modified at C1 and/or C3 with an amino group were synthesized to study the influence of the substitution of one or both hydroxyl groups of A‐ring by amino groups on the affinity for vitamin D receptor (VDR) and vitamin D binding protein (hDBP), and also on the antiproliferative activity. The A‐ring precursors were prepared from cis,cis‐1,3,5‐cyclohexanetriol applying a desymmetrization reaction of a prochiral 1,3‐diol catalyzed by Pseudomonas cepacia lipase as a key step. The structural elucidation of diastereoisomers were unambiguously assigned by NMR spectroscopy.magnified image
Disruption of Zinc Homeostasis by a Novel Platinum(IV)‐Terthiophene Complex for Antitumor Immunity
Authors: Su Xuxian , Liu Bin , Wang Wen‐Jin , Peng Kun , Liang Bing‐Bing , Zheng Yue , Cao Qian , Mao Zong‐Wan 
Published: December 2022

AbstractZinc homeostatic medicine is of great potential for cancer chemo‐immunotherapy; however, there are few reports on antitumor compounds that can trigger Zn2+‐mediated immune responses. In this work, we developed a novel cyclometalated PtIV‐terthiophene complex,Pt3, that not only induces DNA damage and cellular metabolism dysregulation, but also disrupts zinc homeostasis as indicated by the abnormal transcriptional level of zinc regulatory proteins, excess accumulation of Zn2+in cytoplasm, and down‐regulation of metallothioneins (MTs), which further caused redox imbalance. The simultaneous disruption of zinc and redox homeostasis in response toPt3treatment activated gasdermin‐D mediated pyroptosis accompanied by cytoskeleton remodeling, thus releasing pro‐inflammatory cytokines to promote dendritic cell (DC) maturation and T cell tumor‐infiltration, eventually eliminating both primary and distant tumors in vivo. As far as we know, this is the first metal complex that can regulate zinc homeostasis to activate antitumor immunity.
Design of intelligence‐based optimized adaptive fuzzy PID controllers for a two chamber microbial fuel cell
Authors: Eren Berkay , Demir Mehmet Hakan 
Published: December 2022

AbstractThe output voltage of microbial fuel cells (MFCs) needs to be controlled effectively to improve the operating efficiency of MFC system against the load variations, disturbances, and uncertainties. The output voltage control is purposed to provide the MFC with an appropriate amount of fuel required to maintain the stability of output voltage. In the applications, the MFC output voltage can be requested to track the variable reference voltage or to track the constant output voltage under changing conditions such as load change. For this purpose, two adaptive fuzzy PID (FPID) controllers powered by optimization algorithms were designed in this study to keep the output voltage value of the MFC at the desired values. This study extends the previous works by using optimization algorithms, such as particle swarm optimization (PSO) and gray wolf optimization (GWO) algorithms, to adjust fuzzy logic parameters, which are used for tuning Proportional‐Integral‐Derivative (PID) controllers. The optimization‐based adaptive FPID controllers play an active role in efficient, fast, and robust tracking of the reference voltage value with its adaptive structure. The designed adaptive control algorithms were tested under different cases, which involve the variation of the reference voltage and load conditions. The results show that both of these controllers can effectively control the output voltage of a MFC by regulating the flow rate of the fuel. In addition, the performances of the designed controller strategies according to the results obtained vary according to the reference signal. While PSO‐based FPID gives more successful results for positive step changes, GWO‐based FPID gives more successful results for negative step changes. These two control strategies show more efficient, robust, successful, and faster performances compared to the traditional PID controller.
Spinosad‐associated modulation of select cytochrome P450s and glutathione S‐transferases in the Colorado potato beetle, Leptinotarsa decemlineata
Authors: Bastarache Pierre , Bouafoura Raed , Omakele Enock , Moffat Chandra E. , Vickruck Jess L. , Morin Pier Jr 
Published: December 2022

AbstractThe Colorado potato beetle (Leptinotarsa decemlineata (Say)) is an insect pest that threatens potato crops. Multiple options exist to limit the impact of this pest even though insecticides remain a primary option for its control. Insecticide resistance has been reported in Colorado potato beetles and a better understanding of the molecular players underlying such process is of utmost importance to optimize the tools used to mitigate the impact of this insect. Resistance against the insecticide spinosad has been reported in this insect and this work thus aims at exploring the expression of targets previously associated with insecticide response in Colorado potato beetles exposed to this compound. Amplification and quantification of transcripts coding for cytochrome P450s and glutathione S‐transferases were conducted via qRT‐PCR in insects treated with varying doses of spinosad and for different time duration. This approach notably revealed differential expression of CYP6a23 and CYP12a5 in insects exposed to low doses of spinosad for 4 h as well as modulation of CYP6a13, CYP6d4, GST, GST1, and GST1‐Like in insects treated with high doses of spinosad for the same duration. RNAi‐based targeting of CYP4g15 and CYP6a23 was associated with marked reduction of transcript expression 7 days following dsRNA injection and reduction of the former had a marked impact on insect viability. In general, results presented here provide novel information regarding the expression of transcripts relevant to spinosad response in Colorado potato beetles and reveal a novel target to consider in the development of RNAi‐based strategies aimed at this potato pest.
Increased resting‐state thalamocortical functional connectivity in children and young adults with autism spectrum disorder
Authors: Baran Bengi , Nguyen Quynh Trang Huong , Mylonas Dimitrios , Santangelo Susan L. , Manoach Dara S. 
Published: December 2022

AbstractThere is converging evidence that abnormal thalamocortical interactions contribute to attention deficits and sensory sensitivities in autism spectrum disorder (ASD). However, previous functional MRI studies of thalamocortical connectivity in ASD have produced inconsistent findings in terms of both the direction (hyper vs. hypoconnectivity) and location of group differences. This may reflect, in part, the confounding effects of head motion during scans. In the present study, we investigated resting‐state thalamocortical functional connectivity in 8–25 year‐olds with ASD and their typically developing (TD) peers. We used pre‐scan training, on‐line motion correction, and rigorous data quality assurance protocols to minimize motion confounds. ASD participants showed increased thalamic connectivity with temporal cortex relative to TD. Both groups showed similar age‐related decreases in thalamic connectivity with occipital cortex, consistent with a process of circuit refinement. Findings of thalamocortical hyperconnectivity in ASD are consistent with other evidence that decreased thalamic inhibition leads to increase and less filtered sensory information reaching the cortex where it disrupts attention and contributes to sensory sensitivity. This literature motivates studies of mechanisms, functional consequences, and treatment of thalamocortical circuit dysfunction in ASD.
αCT1 peptide sensitizes glioma cells to temozolomide in a glioblastoma organoid platform
Authors: Che Jingru , DePalma Thomas J. , Sivakumar Hemamylammal , Mezache Louisa S. , Tallman Miranda M. , Venere Monica , Swindle‐Reilly Katelyn , Veeraraghavan Rengasayee , Skardal Aleksander 
Published: December 2022

AbstractGlioblastoma (GBM) is the most common form of brain cancer. Even with aggressive treatment, tumor recurrence is almost universal and patient prognosis is poor because many GBM cell subpopulations, especially the mesenchymal and glioma stem cell populations, are resistant to temozolomide (TMZ), the most commonly used chemotherapeutic in GBM. For this reason, there is an urgent need for the development of new therapies that can more effectively treat GBM. Several recent studies have indicated that high expression of connexin 43 (Cx43) in GBM is associated with poor patient outcomes. It has been hypothesized that inhibition of the Cx43 hemichannels could prevent TMZ efflux and sensitize otherwise resistance cells to the treatment. In this study, we use a three‐dimensional organoid model of GBM to demonstrate that combinatorial treatment with TMZ and αCT1, a Cx43 mimetic peptide, significantly improves treatment efficacy in certain populations of GBM. Confocal imaging was used to visualize changes in Cx43 expression in response to combinatorial treatment. These results indicate that Cx43 inhibition should be pursued further as an improved treatment for GBM.
In Search of Hosts for Blue OLEDs: Computational Design and Experimental Validation
Authors: Thakur Diksha , Ram Nagar Mangey , Kumar Sunil , Shahnawaz  , Tomar Anju , Karmakar Anirban , Banik Subrata , Jou Jwo‐Huei , Ghosh Subrata 
Published: December 2022

AbstractConsidering the difficulties associated with the conventional ‘trial and error’ method for a complete analysis of a giant molecular space, we took the aid of computational pathway (DFT) in screening a large space search of 780 (12×13×5) molecules to search for a host for the blue emitter. The selection process was completed in three Tiers with the conditions of highest theoretical triplet energy (>2.81 eV), aligned HOMO/LUMO levels w.r.t blue dopant (FIrpic), and position of substituents to meet the optimal requirements as host materials. Tier 1 screened twelve different imidazole heterocycle derivatives as base space groups which resulted in the selection of 4,5‐diphenyl‐1H‐imidazole. Tier 2 process converged the search to mCN‐CZ having the highest triplet energy and appropriate HOMO/LUMO level relative to FIrpic and ETL. Further, the carbazole of mCN‐CZ was replaced with different aromatic hydrocarbons to find the other best compound in terms of triplet energy and HOMO/LUMO. Tier 3 resulted in another promising candidate (mCN‐FL) as possible host materials. The band alignment with guest predicted mCN‐FL and mCN‐CZ to have optimal device performances compared to CZ‐CZ and the experimentally observed device performance was in accordance with virtual screening results when TAPC was utilized as the hole transporter. The device results of mCN‐CZ and mCN‐FL were better than the reference host TCTA. The obtained results thus proved that a virtual screening process will be a useful tool for synthetic chemists in designing task‐specific materials.
Fe‐Catalyzed Aliphatic C−H Methylation of Glycine Derivatives and Peptides
Authors: Song Silin , Cheng Xiuliang , Cheng Shiyan , Lin Yu‐Mei , Gong Lei 
Published: December 2022

AbstractDirect and selective C−H methylation is a powerful tool with which to install methyl groups into organic molecules, and is particularly useful in pharmaceutical chemistry. However, practical methods for such modification of biologically interesting targets have been rarely developed. We here report an iron‐catalyzed C(sp3)−H methylation reaction of glycine derivatives, peptides and drug‐like molecules in an alcohol in the presence of di‐tert‐butyl peroxide. A readily available iron catalyst plays multiple roles in the transformation, which accelerates oxidation of C−N bonds to C=N double bonds, activates imine intermediates as Lewis acids by bidentate chelation, and at the same time facilitates cleavage of the peroxide to generate methyl radicals. A variety of methylated N‐aryl glycine derivatives and peptides were obtained in good yield and with excellent chemo‐ and site‐selectivity. This reaction is scalable, easily managed, and can be completed within 1–2 h. It features an economic, bio‐friendly catalyst, a green solvent and low toxic reagents, and will provide effective access to precise C−H modification of biomolecules and natural products.
l‐Serine is the Direct Precursor for the Pyrazine Ring Construction in the Biosynthesis of 3‐Isobutyl‐2‐Methoxypyrazine in Bell Pepper Fruits (Capsicum annuum L.)
Authors: Zamolo Francesca , Wüst Matthias 
Published: December 2022

Abstract3‐Isobutyl‐2‐methoxypyrazine (IBMP) is an extremely potent odorant and responsible for the specific aroma of many fruits and vegetables. Especially bell pepper contains high levels of IBMP, which is the character impact compound of its typical aroma. However, since the discovery of methoxypyrazines in plants in the 1960s the biosynthesis of their pyrazine ring motif remained so far unknown. Therefore, the biosynthetic pathway to IBMP was investigated by feeding experiments with stable‐isotope labeled precursors. For the first time it could be shown that l‐serine plays a key role in the pyrazine ring construction of 3‐alkyl‐2‐methoxypyrazines (MPs). Based on HS‐SPME‐GCxGC‐TOF‐MS analysis, it is shown that the biosynthetic pathway to IBMP is closely linked to photorespiratory derived l‐serine.