bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chidamide plus envafolimab as subsequent treatment in advanced non‐small cell lung cancer patients resistant to anti‐PD‐1 therapy: A multicohort, open‐label, phase II trial with biomarker analysis
Authors: Zhang Yaxiong , Chen Zihong , Liu Yu , Han Liang , Jiang Wei , Wang Qiming , Shi Jianhua , Lu Liqin , Li Jianying , Zhang Mingjun , Huang Yan , Yang Yunpeng , Hou Xue , Zhang Li , Li Jing , Fang Wenfeng , Chen Gang 
Published: April 2024

AbstractBackgroundCombination of chidamide and anti‐PD‐L1 inhibitor produce synergistic anti‐tumor effect in advanced NSCLC patients resistant to anti‐PD‐1 treatment. However, the effect of chidamide plus envafolimab has not been reported.AimsThis study aimed to evaluate the efficacy of chidamide plus envafolimab in advanced NSCLC patients resistant toanti‐PD‐1 treatment.Materials and MethodsEligible advanced NSCLC patients after resistant to anti‐PD‐1 therapy received chidamide and envafolimab. The primary endpoint was objective response rate (ORR). The secondary end points included disease control rate (DCR), progression‐free survival (PFS), and safety. The expression of histone deacetylase 2 (HDAC2), PD‐L1, and blood TMB (bTMB) was also analyzed.ResultsAfter a median follow‐up of 8.1 (range: 7.6–9.2) months, only two patients achieved partial response. The ORR was 6.7% (2/30), DCR was 50% (15/30), and median PFS (mPFS) was 3.5 (95% confidence interval: 1.9–5.5) months. Biomarker analysis revealed that patients with high‐level HDAC2 expression had numerically superior ORR (4.3% vs. 0), DCR (52.2% vs. 0) and mPFS (3.7 vs. 1.4m). Patients with negative PD‐L1 had numerically superior DCR (52.2% vs. 33.3%) and mPFS (3.7m vs. 1.8m), so were those with low‐level bTMB (DCR: 59.1% vs. 16.7%, mPFS: 3.8 vs.1.9m). Overall safety was controllable.DiscussionHigh HDAC2patients showed better ORR, DCR, and PFS. In addition, patient with negative PD‐L1 and low‐level bTMB had better DCR and PFS. This may be related to the epigenetic function of chidamide. However, the sample size was not big enough, so it is necessary to increase sample size to confirm the conclusion.ConclusionCombination of chidamide and envafolimab showed efficacy signals in certain NSCLC patients. But further identification of beneficial population is necessary for precision treatment.
Atypical chemokine receptor 4 (ACKR4/CCX‐CKR): A comprehensive exploration across physiological and pathological landscapes in contemporary research
Authors: Naser Israa Habeeb , Hamza Asia Ali , Alhili Ahmed , Faisal Ahmed Naser , Ali Mohammed Shnain , Kadhim Noor Abdulaala , Suliman Muath , Alshahrani Mohammad Y. , Alawadi Ahmed 
Published: April 2024

AbstractAtypical chemokine receptor 4 (ACKR4), also known as CCX‐CKR, is a member of the chemokine receptor family that lacks typical G protein signaling activity. Instead, ACKR4 functions as a scavenger receptor that can bind and internalize a wide range of chemokines, influencing their availability and activity in the body. ACKR4 is involved in various physiological processes, such as immune cell trafficking and the development of thymus, spleen, and lymph nodes. Moreover, ACKR4 has been implicated in several pathological conditions, including cancer, heart and lung diseases. In cancer, ACKR4 plays a complex role, acting as a tumor suppressor or promoter depending on the type of cancer and the stage of the disease. For instance, ACKR4 may inhibit the growth and metastasis of breast cancer, but it may also promote the progression of hepatocellular carcinoma and gastric cancer. In inflammatory situations, ACKR4 has been found to modulate the recruitment and activation of immune cells, contributing to the pathogenesis of diseases such as myocardial infraction and pulmonary sarcoidosis. The study of ACKR4 is still ongoing, and further research is needed to fully understand its role in different physiological and pathological contexts. Nonetheless, ACKR4 represents a promising target for the development of novel therapeutic strategies for various diseases.
Host‐Guest Stimuli‐Responsive Click Chemistry
Authors: Blanco‐Gómez Arturo , Díaz‐Abellás Mauro , Montes de Oca Iván , Peinador Carlos , Pazos Elena , García Marcos D. 
Published: April 2024

AbstractClick chemistry has reached its maturity as the weapon of choice for the irreversible ligation of molecular fragments, with over 20 years of research resulting in the development or improvement of highly efficient kinetically controlled conjugation reactions. Nevertheless, traditional click reactions can be disadvantageous not only in terms of efficiency (side products, slow kinetics, air/water tolerance, etc.), but also because they completely avoid the possibility to reversibly produce and control bound/unbound states. Recently, non‐covalent click chemistry has appeared as a more efficient alternative, in particular by using host‐guest self‐assembled systems of high thermodynamic stability and kinetic lability. This review discusses the implementation of molecular switches in the development of such non‐covalent ligation processes, resulting in what we have termed stimuli‐responsive click chemistry, in which the bound/unbound constitutional states of the system can be favored by external stimulation, in particular using host‐guest complexes. As we exemplify with handpicked selected examples, these supramolecular systems are well suited for the development of human‐controlled molecular conjugation, by coupling thermodynamically regulated processes with appropriate temporally resolved extrinsic control mechanisms, thus mimicking nature and advancing our efforts to develop a more function‐oriented chemical synthesis.
On the Synthesis and Structure of ‘Naked’ Ga(I) and In(I) Salts and the Surprising Stability of Simple Ga(I) and In(I) Salts in the Coordinating Solvents Ether and Acetonitrile
Authors: Barthélemy Antoine , Scherer Harald , Weller Hanna , Krossing Ingo 
Published: April 2024

AbstractIn this work, we present the solid‐state structures of solvent‐free Ga[pf] and In[pf] salts ([pf]−=[Al(ORF)4]−; RF=C(CF3)3), which are very rare examples of salts with truly ‘naked’ metal cations. Both salts may serve as starting materials for subvalent gallium and indium chemistry with very weakly coordinating ligands providing the freedom of choice for solvents and ligands for the future. On the other hand, we report and rationalize the formation and isolation of [M(OEt2)2][pf] and [M(MeCN)2][pf] (M=Ga, In), underlining the surprising stability of these subvalent group 13 M+ ions against disproportionation. Unexpectedly, dicoordinate and carbene analogous [M(L)2]+ ions with the [pf]− counterion are stable in L=acetonitrile and diethyl ether at room temperature, opening up possible applications for example in organic synthesis and catalysis.
Prediction of Acute Hepatotoxicity With Human Pluripotent Stem Cell‐Derived Hepatic Organoids
Authors: Kim Hyemin , Kim Sang Kyum , Oelgeschläger Michael , Park Han‐Jin 
Published: April 2024

AbstractRecent development of hepatic organoids (HOs) derived from human pluripotent stem cells (hPSCs) provides an alternative in vitro model that can mimic the human liver detoxification pathway for drug safety assessment. By recapitulating the high level of maturity and drug‐metabolizing capacity of the liver in a three‐dimensional organoid culture, HOs may allow researchers to assess drug toxicity and metabolism more accurately than animal models or hepatocellular carcinoma cells. Although this promising potential has contributed to the development of various protocols, only a few protocols are available to generate functional HOs with guaranteed CYP450 enzymatic activity, the key feature driving toxic responses during drug metabolism. Based on previously published protocols, we describe an optimized culture method that can substantially increase the expression and activity of CYP450s, in particular CYP3A4, CYP2C9, and CYP2C19, in HOs. To generate mass‐produced and highly reproducible HOs required as models for toxicity evaluation, we first generated hepatic endodermal organoids (HEOs) from hPSCs capable of in vitro proliferation and cryopreservation. The stepwise protocol includes generating HEOs as well as efficient methods to enhance CYP450 expression and activity in terminally differentiated HOs. Furthermore, we present a simple protocol for the assessment of HO cytotoxicity, one of the hallmarks of drug‐induced acute hepatotoxicity. The protocols are relatively straightforward and can be successfully used by laboratories with basic experience in culturing hPSCs. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC.Basic Protocol 1: Generation of hepatic endodermal organoids from human pluripotent stem cellsBasic Protocol 2: Expansion and cryopreservation of hepatic endodermal organoidsBasic Protocol 3: Differentiation of hepatic organoids from hepatic endodermal organoidsBasic Protocol 4: Evaluation of hepatotoxicity using hepatic organoidsSupport Protocol: Human pluripotent stem cell culture
Evaluation of variation in seedling root architectural traits and their potential association with nitrogen fixation and agronomic traits in field pea accessions
Authors: Dhillon Loveleen Kaur , Chandnani Rahul , Nakhforoosh Alireza , Qin Tongfei , Panjvani Karim , Feurtado J. Allan , Kochian Leon , Warkentin Thomas D. 
Published: April 2024

AbstractRoot system architecture (RSA) plays a central role in water and nutrient acquisition in plants. Plasticity and genetic variation in RSA can be used as an adaptive strategy to optimize plant performance under variable environments. We quantified phenotypic variation for seedling RSA among 44 diverse pea (Pisum sativum L.) genotypes, including breeding lines and germplasm accessions, grown under controlled conditions for 14 days using two‐dimensional hydroponic root imaging. Root image analysis revealed significant genotypic variability among the lines for all root traits, namely root length (RL), root diameter (RD), root volume, root surface area, number of tips, network width (NW), network depth (ND), and network convex area. Significant positive correlations were observed among the evaluated root traits, ranging from 0.5 to 0.9. Pea lines were ranked based on estimated means for root traits, with lines E20, F1, and F8 showing high rankings, while E4 and F5 received low rankings for most traits. To associate root traits with nitrogen (N) fixation and field agronomic performance, we performed redundancy analysis (RDA). The quantified root traits accounted for significant variation in the agronomic traits (R2 = ∼30%, p < 0.001). RDA showed a positive association between lodging susceptibility and root system NW and between plant height and root system ND. RD was positively associated with grain yield and N fixation. N fixation was positively associated with the number of lateral roots. The findings of this study indicate that variation for seedling root traits in pea could aid selection for N fixation and other important agronomic traits.
Genetic variation for endosperm carbohydrates and total soluble solids in shrunken2, sugary1, waxy1, and wild‐type near‐isogenic corn lines across three harvest dates
Authors: Wilson Alexa R. , Fiore Isabella G. , McCluskey Cathleen , Tracy William F. 
Published: April 2024

AbstractSweet corn (Zea mays L.) cultivars must meet stringent quality standards to be accepted in the marketplace. Breeding for eating‐quality traits, such as sweetness, typically involves taste ratings or quantification of carbohydrate content. Total soluble solids (TSS) content is used as a proxy for sweetness in many fruit crops. Using a diallel of near‐isogenic corn lines for sugary1, shrunken2, waxy1, and wild‐type (WT) endosperm types, a combining ability analysis for carbohydrate traits and TSS content determined the relationship of these traits over three harvest dates. Variation existed for total sugar, sucrose, glucose, fructose, total polysaccharides, and starch content within and across endosperm types and harvest dates, but strong correlations with TSS content were present only when assessed across all endosperm types. Strong similarities existed among WT, waxy1, and sugary1 near‐isogenic lines for general combining ability for carbohydrate traits, while shrunken2 near‐isogenic lines had different desirable combiners. Line C40 was a desirable general combiner for carbohydrate traits among WT, waxy1, and sugary1 endosperm types, while Ia5125, P39, and Ia453 were desirable general combiners for shrunken2 endosperm. This experiment also determined that TSS content is not a useful trait in sweet corn breeding for quality traits.
Large‐scale breeding population validating significant loci for the 1000‐kernel weight of wheat
Authors: Jiang Peng , Li Chang , Cui Fa , Wu Lei , Zhang Zhaoyang , He Yi , Zhang Peng , Ma Hongxiang , Zhang Xu 
Published: April 2024

AbstractAs an important component of wheat (Triticum aestivum L.) yield, 1000‐kernel weight (TKW) has played a crucial role in yield improvement in recent decades. Marker‐assisted selection is an effective tool for improving quantitative traits; however, most markers have not been effectively applied in TKW improvement despite the identification of many loci associated with TKW. In this study, association mapping was performed using local cultivated varieties, and a previous linkage analysis was integrated to identify 10 candidate intervals. The corresponding kompetitive allele‐specific PCR markers associated with TKW were successfully developed and screened in 1153 F4 breeding lines. Three markers, namely, Ktkw‐5B2, Ktkw‐5D, and Ktkw‐7D, were proved to be significantly related to TKW according to large‐scale association mapping, and their ability to increase TKW was enhanced in combination. We applied the three markers in 150 F6 breeding lines and obtained 25 high‐TKW lines, indicating the availability in marker‐assisted selection. The TKW‐increasing allele for Ktkw‐5D was heavily selected in the present breeding program, while that for Ktkw‐5B2 was low and for Ktkw‐7D tended to increase after 2000. Furthermore, strategies for gene exploration in the three significant intervals were proposed. These results are expected to provide an efficient route for improving TKW in wheat high‐yield breeding.
Addition of Imidazolium‐Based Ionic Liquid to Improve Methanol Production in Polyamine‐Assisted CO2 Capture and Conversion Systems Using Pincer Catalysts
Authors: Koch Christopher J. , Goeppert Alain , Surya Prakash G. K. 
Published: April 2024

AbstractIonic liquids have been studied as CO2 capture agents. However, they are rarely used in combined CO2 capture and conversion processes. Utilizing imidazolium‐based ionic liquids, the conversion of CO2 to methanol was greatly improved in polyamine assisted systems catalyzed by homogeneous pincer catalysts with Ru and Mn metal centers. Among the ionic liquids tested, [BMIM]OAc was found to perform the best under the given reaction conditions. Among the polyamine tested, pentaethylenehexamine (PEHA) led to the highest conversion rates. Ru‐Macho and Ru‐Macho‐BH were the most active catalysts. Direct air capture utilizing PEHA as the capture material was also demonstrated and produced an 86 % conversion of the captured CO2 to methanol in the presence of [BMIM]OAc.
Outcomes of 6‐mm diameter fully covered self‐expandable metal stents for preoperative biliary drainage in pancreatic cancer
Authors: Nakagawa Hiroki , Takeda Tsuyoshi , Okamoto Takeshi , Mie Takafumi , Kasuga Akiyoshi , Sasaki Takashi , Ozaka Masato , Matsuda Takahisa , Igarashi Yoshinori , Sasahira Naoki 
Published: April 2024

AbstractBackground10‐mm self‐expandable metal stents (SEMSs) are commonly used for preoperative biliary drainage in pancreatic cancer. However, smaller diameter SEMSs have attracted attention with the attempt to reduce stent‐related adverse events (AEs).MethodsWe retrospectively analyzed consecutive borderline resectable pancreatic cancer patients who underwent neoadjuvant therapy and fully covered SEMS (FCSEMS) placement from April 2015 to May 2023. The primary outcome was stent‐related non‐event rate (NER), which was defined as the rate of completion of surgery without developing any preoperative events (recurrent biliary obstruction [RBO] or stent‐related AEs). Secondary outcomes included stent‐related AEs, causes of RBO, and cumulative incidence of RBO. Risk factors for pancreatitis, RBO, and stent migration were also examined.ResultsA total of 76 patients were included (6‐mm group: 23; 10‐mm group: 53). Stent‐related NER (57% vs. 64%, p = 0.610), stent‐related AEs (4% vs. 15%, p = 0.263), overall RBO rates (39% vs. 23%, p = 0.168), cumulative incidence of RBO (hazard ratio, 2.24; 95% confidence interval, 0.95–5.25; p = 0.065) were not significantly different between the two groups. Tumor involvement of the pancreatic duct was identified as a risk‐reducing factor for pancreatitis, while an FCSEMS diameter of 6 mm was not identified as a risk factor for RBO and stent migration.ConclusionsStent‐related NER was not significantly affected by FCSEMS diameter. Further studies are needed to confirm the usefulness of 6‐mm diameter FCSEMS for preoperative biliary drainage in patients with borderline resectable pancreatic cancer.
Optimal sampling interval for characterisation of the circadian rhythm of body temperature in homeothermic animals using periodogram and cosinor analysis
Authors: Goh Grace , Vesterdorf Kristine , Fuller Andrea , Blache Dominique , Maloney Shane K. 
Published: April 2024

AbstractCore body temperature (Tc) is a critical aspect of homeostasis in birds and mammals and is increasingly used as a biomarker of the fitness of an animal to its environment. Periodogram and cosinor analysis can be used to estimate the characteristics of the circadian rhythm of Tc from data obtained on loggers that have limited memory capacity and battery life. The sampling interval can be manipulated to maximise the recording period, but the impact of sampling interval on the output of periodogram or cosinor analysis is unknown. Some basic guidelines are available from signal analysis theory, but those guidelines have never been tested on Tc data. We obtained data at 1‐, 5‐ or 10‐min intervals from nine avian or mammalian species, and re‐sampled those data to simulate logging at up to 240‐min intervals. The period of the rhythm was first analysed using the Lomb–Scargle periodogram, and the mesor, amplitude, acrophase and adjusted coefficient of determination (R2) from the original and the re‐sampled data were obtained using cosinor analysis. Sampling intervals longer than 60 min did not affect the average mesor, amplitude, acrophase or adjusted R2, but did impact the estimation of the period of the rhythm. In most species, the period was not detectable when intervals longer than 120 min were used. In all individual profiles, a 30‐min sampling interval modified the values of the mesor and amplitude by less than 0.1°C, and the adjusted R2 by less than 0.1. At a 30‐min interval, the acrophase was accurate to within 15 min for all species except mice. The adjusted R2 increased as sampling frequency decreased. In most cases, a 30‐min sampling interval provides a reliable estimate of the circadian Tc rhythm using periodogram and cosinor analysis. Our findings will help biologists to select sampling intervals to fit their research goals.
Where east meets west: Phylogeography of the high Arctic North American brant goose
Authors: Wilson Robert E. , Boyd W. Sean , Sonsthagen Sarah A. , Ward David H. , Clausen Preben , Dickson Kathryn M. , Ebbinge Barwolt S. , Gudmundsson Gudmundur A. , Sage George K. , Rearick Jolene R. , Derksen Dirk V. , Talbot Sandra L. 
Published: April 2024

AbstractGenetic variation in Arctic species is often influenced by vicariance during the Pleistocene, as ice sheets fragmented the landscape and displaced populations to low‐ and high‐latitude refugia. The formation of secondary contact or suture zones during periods of ice sheet retraction has important consequences on genetic diversity by facilitating genetic connectivity between formerly isolated populations. Brant geese (Branta bernicla) are a maritime migratory waterfowl (Anseriformes) species that almost exclusively uses coastal habitats. Within North America, brant geese are characterized by two phenotypically distinct subspecies that utilize disjunct breeding and wintering areas in the northern Pacific and Atlantic. In the Western High Arctic of Canada, brant geese consist of individuals with an intermediate phenotype that are rarely observed nesting outside this region. We examined the genetic structure of brant geese populations from each subspecies and areas consisting of intermediate phenotypes using mitochondrial DNA (mtDNA) control region sequence data and microsatellite loci. We found a strong east–west partition in both marker types consistent with refugial populations. Within subspecies, structure was also observed at mtDNA while microsatellite data suggested the presence of only two distinct genetic clusters. The Western High Arctic (WHA) appears to be a secondary contact zone for both Atlantic and Pacific lineages as mtDNA and nuclear genotypes were assigned to both subspecies, and admixed individuals were observed in this region. The mtDNA sequence data outside WHA suggests no or very restricted intermixing between Atlantic and Pacific wintering populations which is consistent with published banding and telemetry data. Our study indicates that, although brant geese in the WHA are not a genetically distinct lineage, this region may act as a reservoir of genetic diversity and may be an area of high conservation value given the potential of low reproductive output in this species.
Comparative reproductive ecology of Old and New World Trogons, an order in decline across the world
Authors: Şahin Arslan Necmiye , Martin Thomas E. 
Published: April 2024

AbstractMany tropical species show declining populations. The pantropical order Trogoniformes has 76% of its species ranked as declining, reflecting a worldwide problem. Here, we report on the reproductive ecology and life history traits of the declining and near‐threatened old world Whitehead's Trogon (Harpactes whiteheadi), the declining new world Collared Trogon (Trogon collaris), and the stable Masked Trogon (T. personatus). We also reviewed the literature on reproductive ecology and life history traits of trogons to assess possible commonalities that might help explain population declines. We found that the declining Whitehead's and Collared Trogons had reasonable nest success (32% and 25%, respectively), while the stable Masked Trogon had poor reproductive success (9%), all contrary to population trends. However, the limited literature data suggested that poor reproductive success may be common among trogons, which may contribute to population declines. Parents fed young at a low rate and had long on‐bouts for incubation and nestling warming that reduced activity at the nest, as favored by high nest predation risk over evolutionary time. We found that young fledged from the nest with poorly developed wings, as also favored by high nest predation risk. Evolved nestling periods among trogon species suggests that poor wing development is likely common. Wing development has been shown to affect juvenile survival after leaving the nest. The poor wing development may be an important contributor to population declines that deserves more attention. Evolved life history traits are important to recognize as creating population vulnerabilities in a changing world.