bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring Genes and Phenotypes Within Chromosomal Regions Using OMIM's GeneScout
Authors: Applegate Carolyn D. , Schiettecatte François , Hamosh Ada , Amberger Joanna S. 
Published: September 2022

AbstractStructural variation in genomes, such as copy number variants (CNVs), is under scrutiny for its contribution to phenotypic expression and evolution. Regions of homozygosity (ROH) are ripe for phenotype‐gene discovery. Determining the genes and related phenotypes within genomic regions is key to studying potential functional and phenotypic consequences. Because individuals have multiple CNVs and ROHs in their genome, identifying genomic regions that are phenotypically significant is challenging. GeneScout is a web‐based tool that can be used to search genomic regions to display and filter the genes and their associated phenotypes within regions of interest. Phenotypes and their associated gene(s) can then be filtered to show only the genes with phenotypes that have a particular inheritance pattern and/or specific clinical feature(s). Phenotypes can then be selected to compare the clinical synopses side‐by‐side in Online Mendelian Inheritance in Man (OMIM®). Additionally, two coordinate sets can be compared to determine either the regions of overlap or the unique regions (subtraction). The resulting coordinate ranges are displayed on the results page, and the results table displays only the genes and phenotypes present within the coordinate ranges. The interactive table includes gene‐specific links to external resources such as ClinVar, ClinGen validity, ClinGen dosage, and gnomAD, and a diamond symbol next to the gene name indicates a gene that spans the start or end of a coordinate range. Searches and comparisons may be performed for coordinates in assemblies GRCh37 (hg19) and GRCh38 (hg38). The results page offers the option to liftover coordinates entered in GRCh37 to GRCh38 and updates the results table to display the gene content based on assembly GRCh38. The search coordinates and results table can be downloaded in a tab‐delimited or Excel file. © 2022 Wiley Periodicals LLC.Basic Protocol: Searching GeneScout
Potential significance of uncovered self‐expandable metal stents for distal malignant biliary obstruction: A propensity score‐adjusted competing risk regression analysis
Authors: Torisu Yuichi , Chiba Masafumi , Kato Masayuki , Kinoshita Yuji , Akasu Takafumi , Kanai Tomoya , Tomita Yoichi , Shimamoto Nana , Abe Takahiro , Kanazawa Keisuke , Tsukinaga Shintaro , Nakano Masanori , Saeki Chisato , Sumiyama Kazuki , Saruta Masayuki 
Published: September 2022

AbstractObjectivesSelection criteria for self‐expandable metal stents (SEMSs) with or without cover during palliative treatment of distal malignant biliary obstruction (DMBO) remain unclear. We evaluated factors associated with time to recurrent biliary obstruction (TRBO) in fully covered SEMSs (FCSEMSs) and uncovered SEMSs (UCSEMSs).MethodsWe retrospectively analyzed consecutive patients with DMBO who received a SEMS. TRBO was determined using the Kaplan–Meier analysis, and complications were compared between the FCSEMS and UCSEMS groups. After TRBO‐associated factors were extracted using multivariate competing‐risks regression (CRR), propensity score‐adjusted CRRs were performed to verify their robustness.ResultsThere were 180 patients (66 FCSEMSs and 114 UCSEMSs) enrolled in this study. There was no significant difference between median TRBO in the FCSEMS and UCSEMS groups (275 vs. 255 days, p = 0.67). Complications were more frequent in the FCSEMS than UCSEMS group (21.2% vs. 8.8%; p = 0.023). Multivariate CRR for TRBO‐associated factors revealed that “pancreatic ductal carcinoma (PDAC) treated with UCSEMS” was the only independent predictor of TRBO (p = 0.03). Similarly, the propensity score‐adjusted CRRs showed no significant difference in TRBO in “FCSEMS” vs “UCSEMS” (p = 0.96); however, there was a significant difference in “PDAC using UCSEMS” vs “other” (p = 0.043). In the palliative care group including any DMBO without chemotherapy, the first quartile of the TRBO of UCSEMS was 100 days.ConclusionsUCSEMSs are a possible option for both patients with DMBO arising from PDAC and for patients with any DMBO receiving palliative care who should avoid SEMS‐related complications.
Past climatic refugia and landscape resistance explain spatial genetic structure in Oriental beech in the South Caucasus
Authors: Sękiewicz Katarzyna , Danelia Irina , Farzaliyev Vahid , Gholizadeh Hamid , Iszkuło Grzegorz , Naqinezhad Alireza , Ramezani Elias , Thomas Peter A. , Tomaszewski Dominik , Walas Łukasz , Dering Monika 
Published: September 2022

AbstractPredicting species‐level effects of climatic changes requires unraveling the factors affecting the spatial genetic composition. However, disentangling the relative contribution of historical and contemporary drivers is challenging. By applying landscape genetics and species distribution modeling, we investigated processes that shaped the neutral genetic structure of Oriental beech (Fagus orientalis), aiming to assess the potential risks involved due to possible future distribution changes in the species. Using nuclear microsatellites, we analyze 32 natural populations from the Georgia and Azerbaijan (South Caucasus). We found that the species colonization history is the most important driver of the genetic pattern. The detected west–east gradient of genetic differentiation corresponds strictly to the Colchis and Hyrcanian glacial refugia. A significant signal of associations to environmental variables suggests that the distinct genetic composition of the Azerbaijan and Hyrcanian stands might also be structured by the local climate. Oriental beech retains an overall high diversity; however, in the context of projected habitat loss, its genetic resources might be greatly impoverished. The most affected are the Azerbaijan and Hyrcanian populations, for which the detected genetic impoverishment may enhance their vulnerability to environmental change. Given the adaptive potential of range‐edge populations, the loss of these populations may ultimately affect the specie's adaptation, and thus the stability and resilience of forest ecosystems in the Caucasus ecoregion. Our study is the first approximation of the potential risks involved, inducing far‐reaching conclusions about the need of maintaining the genetic resources of Oriental beech for a species' capacity to cope with environmental change.
Double Prins Cyclisation Enabled Rapid Access to α,ω‐Hydroxytetrahydropyrans
Authors: Trevorrow Jonathan , O'Kearney‐McMullan Anne , Miller Potucka Lucie , Dobbs Adrian P. 
Published: September 2022

AbstractThe spiroketal moiety is an important substructure within many biological natural products. One method to access them is via the oxidative cyclisation of a pendant hydroxyl group on to a pre‐formed pyran. However access to such precursors has hitherto been challenging and requires multistep syntheses frequently with considerable protecting group manipulation. Herein we report a novel and high yielding method for the preparation of hydroxydi‐ and hydroxytetra‐hydropyrans, as spiroketal precursors, utilizing a novel double‐Prins cyclisation approach.
Solid‐State Direct Electrophilic Selenocyanation of (Hetero)Arenes using Mechanochemistry
Authors: Xiao Jun‐An , Liang Jin‐Shao , Zhang Huan , Meng Ru‐Fang , Su Wei , Lin Chenxiang , Cui Jian‐Guo , Huang Yan‐Min 
Published: September 2022

AbstractA mechanochemical direct selenocyanation of arenes/heterocyclic arenes with electrophilic selenocyanating reagents to access (hetero)aryl selenocyanates has been developed. This protocol provided an efficient strategy to access various aromatic selenocyanates in yields up to 99 % under ball‐milling reaction conditions within 60 minutes. Gram‐scale reaction and further transformations of the product were conducted to demonstrate the synthetic utilities of this method.
Electrochemical Sensor for Selective Detection of Meldonium in Urine by Voltammetry
Authors: Mezentseva Olga L. , Slepchenko Galina B. , Dorozhko Elena V. , Moiseeva Eugenia S. , Kryukovskiy Vladimir P. , Zaycev Nikolay K. 
Published: September 2022

AbstractA highly sensitive electrochemical sensor based on arenediazonium tosylates was designed to detect meldonium in urine. The effect of the concentration of ArN2+OTs− arenediazonium tosylate modifier and various substituents was studied. Basic operating parameters for voltammetric meldonium detection were established and the procedure for urine sample preparation was developed. The following values were obtained: limit of detection (LOD) 0.005 mg ⋅ L−1 (P=0.95) and limit of quantification (LOQ) 0.01 mg ⋅ L−1. The relationship between the analytical signal and meldonium concentration in the solution ranging from 0.01 to 400 mg ⋅ L−1 was described by a linear function. The meldonium concentration error did not exceed 18 %. The analysis time for a single urine sample was reduced to 15 minutes.
Studies of Phenol Electrooxidation Performed on Platinum Electrode in Dimethyl Sulphoxide Medium. Determination of Unreacted Phenol by the Effect of 4‐Vinylbenzenesulphonate on the Electrooxidation Process
Authors: Kiss László , Kunsági‐Máté Sándor , Szabó Péter 
Published: September 2022

AbstractThe electrooxidation of phenol was studied in the presence of sodium 4‐vinylbenzenesulfonate in various quantities. When the sulphonate was dissolved in equal or higher quantities than phenol the peak currents increased gradually and suppression of electropolymerization was observed. When the sulphonate quantity was smaller than that of phenol brown films fouled the electrode. The observed phenomenon was utilized in an analytical procedure namely determination of unreacted phenol in electrolysis solution with linear dynamic range between 0 and 50 mM and 2.96 mM detection limit. The shape of curve became saturated‐like above 50 mM.
Metal‐organic framework derived porous structures towards lithium rechargeable batteries
Authors: Han Sang A , Qutaish Hamzeh , Lee Jong‐Won , Park Min‐Sik , Kim Jung Ho 
Published: September 2022

AbstractBatteries are a promising technology in the field of electrical energy storage and have made tremendous strides in recent few decades. In particular, lithium‐ion batteries are leading the smart device era as an essential component of portable electronic devices. From the materials aspect, new and creative solutions are required to resolve the current technical issues on advanced lithium (Li) batteries and improve their safety. Metal‐organic frameworks (MOFs) are considered as tempting candidates to satisfy the requirements of advanced energy storage technologies. In this review, we discuss the characteristics of MOFs for application in different types of Li batteries. A review of these emerging studies in which MOFs have been applied in lithium storage devices can provide an informative blueprint for future MOF research on next‐generation advanced energy storage devices.image
Omnibus or Ominous immigration laws? Immigration policy and mental health of the Hispanic population
Authors: Luo Tianyuan , Kostandini Genti 
Published: September 2022

AbstractThis study examines the impact of Omnibus Immigration Laws on the mental health of the Hispanic populations in the U.S. We use a Difference‐in‐Differences framework and data from the Behavioral Risk Factor Surveillance System Survey of Centers for Disease Control and Prevention for the 2000–2016 period that contains information on more than 400 thousand Hispanics residing in the U.S. We find that the most stringent provision, namely, “show me your papers” laws, adversely affects the mental health of Hispanics and contributes to an increase of 12%–16% in the number of unhealthy mental days and an increase of 13%–18% in the probability of having frequent mental distress in the states with “show me your papers” laws. OIL provisions that enforced the use of E‐Verify or limited the use of public benefits to unauthorized immigrants did not have any effect on mental health. The study also examines (1) police stops, (2) physical health, insurance, and employment status, (3) co‐ethnic density, and (4) immigration enforcement awareness as potential mechanisms that could lead to a deterioration in the mental health of Hispanics. The evidence indicates their vulnerability to strict immigration enforcement. The social and public health cost should be carefully evaluated when formulating and implementing immigration policies.
Interleukin‐33 facilitates liver regeneration through serotonin‐involved gut‐liver axis
Authors: Wen Yankai , Emontzpohl Christoph , Xu Long , Atkins Constance L. , Jeong Jong‐Min , Yang Yang , Kim Kangho , Wu Chuan , Akira Shizuo , Ju Cynthia 
Published: September 2022

Background and Aims:
Insufficient liver regeneration causes post‐hepatectomy liver failure and small‐for‐size syndrome. Identifying therapeutic targets to enhance hepatic regenerative capacity remains urgent. Recently, increased IL‐33 was observed in patients undergoing liver resection and in mice after partial hepatectomy (PHx). The present study aims to investigate the role of IL‐33 in liver regeneration after PHx and to elucidate its underlying mechanisms.

Approach and Results:
We performed PHx in IL‐33−/−, suppression of tumorigenicity 2 (ST2)−/−, and wild‐type control mice, and found deficiency of IL‐33 or its receptor ST2 delayed liver regeneration. The insufficient liver regeneration could be normalized in IL‐33−/− but not ST2−/− mice by recombinant murine IL‐33 administration. Furthermore, we observed an increased level of serotonin in portal blood from wild‐type mice, but not IL‐33−/− or ST2−/− mice, after PHx. ST2 deficiency specifically in enterochromaffin cells recapitulated the phenotype of delayed liver regeneration observed in ST2−/− mice. Moreover, the impeded liver regeneration in IL‐33−/− and ST2−/− mice was restored to normal levels by the treatment with (±)‐2,5‐dimethoxy‐4‐iodoamphetamine, which is an agonist of the 5‐hydroxytrytamine receptor (HTR)2A. Notably, in vitro experiments demonstrated that serotonin/HTR2A‐induced hepatocyte proliferation is dependent on p70S6K activation.

Conclusions:
Our study identified that IL‐33 is pro‐regenerative in a noninjurious model of liver resection. The underlying mechanism involved IL‐33/ST2‐induced increase of serotonin release from enterochromaffin cells to portal blood and subsequent HTR2A/p70S6K activation in hepatocytes by serotonin. The findings implicate the potential of targeting the IL‐33/ST2/serotonin pathway to reduce the risk of post‐hepatectomy liver failure and small‐for‐size syndrome.
A comprehensive overview of CRISPR/Cas 9 technology and application thereof in drug discovery
Authors: Khurana Amit , Sayed Nilofer , Singh Vishakha , Khurana Isha , Allawadhi Prince , Rawat Pushkar Singh , Navik Umashanker , Pasumarthi Sravan Kumar , Bharani Kala Kumar , Weiskirchen Ralf 
Published: September 2022

AbstractClustered Regularly Interspaced Short Palindromic Repeat (CRISPR)‐Cas technology possesses revolutionary potential to positively affect various domains of drug discovery. It has initiated a rise in the area of genetic engineering and its advantages range from classical science to translational medicine. These genome editing systems have given a new dimension to our capabilities to alter, detect and annotate specified gene sequences. Moreover, the ease, robustness and adaptability of the CRISPR/Cas9 technology have led to its extensive utilization in research areas in such a short period of time. The applications include the development of model cell lines, understanding disease mechanisms, discovering disease targets, developing transgenic animals and plants, and transcriptional modulation. Further, the technology is rapidly growing; hence, an overlook of progressive success is crucial. This review presents the current status of the CRISPR–Cas technology in a tailor‐made format from its discovery to several advancements for drug discovery alongwith future trends associated with possibilities and hurdles including ethical concerns.
Ginsenoside Rd ameliorates muscle wasting by suppressing the signal transducer and activator of transcription 3 pathway
Authors: Wijaya Yoseph Toni , Setiawan Tania , Sari Ita Novita , Park Keunwan , Lee Chan Hee , Cho Kae Won , Lee Yun Kyung , Lim Jae‐Young , Yoon Jeong Kyo , Lee Sae Hwan , Kwon Hyog Young 
Published: September 2022

AbstractBackgroundThe effects of some drugs, aging, cancers, and other diseases can cause muscle wasting. Currently, there are no effective drugs for treating muscle wasting. In this study, the effects of ginsenoside Rd (GRd) on muscle wasting were studied.MethodsTumour necrosis factor‐alpha (TNF‐α)/interferon‐gamma (IFN‐γ)‐induced myotube atrophy in mouse C2C12 and human skeletal myoblasts (HSkM) was evaluated based on cell thickness. Atrophy‐related signalling, reactive oxygen species (ROS) level, mitochondrial membrane potential, and mitochondrial number were assessed. GRd (10 mg/kg body weight) was orally administered to aged mice (23–24 months old) and tumour‐bearing (Lewis lung carcinoma [LLC1] or CT26) mice for 5 weeks and 16 days, respectively. Body weight, grip strength, inverted hanging time, and muscle weight were assessed. Histological analysis was also performed to assess the effects of GRd. The evolutionary chemical binding similarity (ECBS) approach, molecular docking, Biacore assay, and signal transducer and activator of transcription (STAT) 3 reporter assay were used to identify targets of GRd.ResultsGRd significantly induced hypertrophy in the C2C12 and HSkM myotubes (average diameter 50.8 ± 2.6% and 49.9% ± 3.7% higher at 100 nM, vs. control, P ≤ 0.001). GRd treatment ameliorated aging‐ and cancer‐induced (LLC1 or CT26) muscle atrophy in mice, which was evidenced by significant increases in grip strength, hanging time, muscle mass, and muscle tissue cross‐sectional area (1.3‐fold to 4.6‐fold, vs. vehicle, P ≤ 0.05; P ≤ 0.01; P ≤ 0.001). STAT3 was found to be a possible target of GRd by the ECBS approach and molecular docking assay. Validation of direct interaction between GRd and STAT3 was confirmed through Biacore analysis. GRd also inhibited STAT3 phosphorylation and STAT3 reporter activity, which led to the inhibition of STAT3 nuclear translocation and the suppression of downstream targets of STAT3, such as atrogin‐1, muscle‐specific RING finger protein (MuRF‐1), and myostatin (MSTN) (29.0 ± 11.2% to 84.3 ± 30.5%, vs. vehicle, P ≤ 0.05; P ≤ 0.01; P ≤ 0.001). Additionally, GRd scavenged ROS (91.7 ± 1.4% reduction at 1 nM, vs. vehicle, P ≤ 0.001), inhibited TNF‐α‐induced dysregulation of ROS level, and improved mitochondrial integrity (P ≤ 0.05; P ≤ 0.01; P ≤ 0.001).ConclusionsGRd ameliorates aging‐ and cancer‐induced muscle wasting. Our findings suggest that GRd may be a novel therapeutic agent or adjuvant for reversing muscle wasting.
Clinical findings of patients with hyperammonemia affected by urea cycle disorders with hepatic encephalopathy
Authors: Lopes Franciele Fátima , Sitta Angela , de Moura Coelho Daniella , Ribas Graziela Schmitt , Faverzani Jéssica Lamberty , dos Reis Bianca Gomes , Wajner Moacir , Vargas Carmen Regla 
Published: September 2022

AbstractUrea cycle disorders (UCD) are a group of genetic diseases caused by deficiencies in the enzymes and transporters involved in the urea cycle. The impairment of the cycle results in ammonia accumulation, leading to neurological dysfunctions and poor outcomes to affected patients. The aim of this study is to investigate and describe UCD patients' principal clinical and biochemical presentations to support professionals on urgent diagnosis and quick management, aiming better outcomes for patients. We explored medical records of 30 patients diagnosed in a referral center from Brazil to delineate UCD clinical and biochemical profile. Patients demonstrated a range of signs and symptoms, such as altered levels of consciousness, acute encephalopathy, seizures, progressive loss of appetite, vomiting, coma, and respiratory distress, in most cases combined with high levels of ammonia, which is an immediate biomarker, leading to a UCD suspicion. The most prevalent UCD detected were ornithine transcarbamylase deficiency, followed by citrullinemia type 1, hyperargininemia, carbamoyl phosphate synthase 1 deficiency, and argininosuccinic aciduria. Clinical symptoms were highly severe, being the majority developmental and neurological disabilities, with 20% of death rate. Laboratory analysis revealed high levels of ammonia (mean ± SD: 860 ± 470 μmol/L; reference value: ≤80 μmol/L), hypoglycemia, metabolic acidosis, and high excretion of orotic acid in the urine (except in carbamoyl phosphate synthetase 1 [CPS1] deficiency). We emphasize the need of urgent identification of UCD clinical and biochemical conditions, and immediate measurement of ammonia, to enable the correct diagnosis and increase the chances of patients' survival, minimizing neurological and psychomotor damage caused by hepatic encephalopathy.
Modulating disease phenotype in a songbird: A role for inflammation in disease tolerance?
Authors: Ruden Rachel M. , Adelman James S. 
Published: September 2022

AbstractIndividual animals vary greatly in their responses to infection, either killing off the invading pathogen (resistance) or minimizing the per‐pathogen costs of infection on host fitness (tolerance). Though we understand little about the physiological drivers of tolerance in wild animals, phenotypically, it manifests as milder clinical signs of disease. Here, we use a well‐described disease system, finch mycoplasmosis, to evaluate the role of inflammation in disease tolerance. House finches (Haemorhous mexicanus) infected with the bacterial pathogen Mycoplasma gallisepticum (MG) develop conjunctival pathology that satisfies the cardinal signs of inflammation. We report on a captive trial performed in 2016 and replicated in 2018 that tested whether chemotherapeutics, specifically nonsteroidal anti‐inflammatory drugs (NSAIDs), can reduce lesion severity, thus pushing individuals toward more tolerant phenotypes. Though birds treated with NSAIDs in the first trial developed milder pathology per unit pathogen load, we found no effect of treatment in the second trial, perhaps due to natural variation in baseline tolerance within the source population across years. Second‐trial control birds developed markedly milder pathology than first‐year controls, suggesting that the effect of trial swamped the effect of treatment in this study. Moving forward, using birds from a population in which the disease is absent or only recently emerged—and so tolerance has not yet been selected for—may better elucidate the role of pro‐inflammatory mediators in disease tolerance.