bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel Autoantibodies in Idiopathic Small Fiber Neuropathy
Authors: Chan Amanda C. Y. , Wong Hiu Yi , Chong Yao Feng , Lai Poh San , Teoh Hock Luen , Ng Alison Y. Y. , Hung Jennifer H. M. , Chan Yee Cheun , Ng Kay W. P. , Vijayan Joy , Ong Jonathan J. Y. , Chandra Bharatendu , Tan Chi Hsien , Rutt Nurul H. , Tan Ti Myen , Ismail Nur Hafiza , Wilder‐Smith Einar , Schwarz Herbert , Choi Hyungwon , Sharma Vijay K. , Mak Anselm
Published: November 2021

Objective

Small fiber neuropathy (SFN) is clinically and etiologically heterogeneous. Although autoimmunity has been postulated to be pathophysiologically important in SFN, few autoantibodies have been described. We aimed to identify autoantibodies associated with idiopathic SFN (iSFN) by a novel high‐throughput protein microarray platform that captures autoantibodies expressed in the native conformational state.

Methods

Sera from 58 SFN patients and 20 age‐ and gender‐matched healthy controls (HCs) were screened against >1,600 immune‐related antigens. Fluorescent unit readout and postassay imaging were performed, followed by composite data normalization and protein fold change (pFC) analysis. Analysis of an independent validation cohort of 33 SFN patients against the same 20 HCs was conducted to identify reproducible proteins in both cohorts.

Results

Nine autoantibodies were screened with statistical significance and pFC criteria in both cohorts, with at least 50% change in serum levels. Three proteins showed consistently high fold changes in main and validation cohorts: MX1 (FC = 2.99 and 3.07, respectively, p = 0.003, q = 0.076), DBNL (FC = 2.11 and 2.16, respectively, p = 0.009, q < 0.003), and KRT8 (FC = 1.65 and 1.70, respectively, p = 0.043, q < 0.003). Further subgroup analysis into iSFN and SFN by secondary causes (secondary SFN) in the main cohort showed that MX1 is higher in iSFN compared to secondary SFN (FC = 1.61 vs 0.106, p = 0.009).

Interpretation

Novel autoantibodies MX1, DBNL, and KRT8 are found in iSFN. MX1 may allow diagnostic subtyping of iSFN patients. ANN NEUROL 2022;91:66–77
Total Synthesis and Late‐Stage C−H Oxidations of ent‐Trachylobane Natural Products
Authors: Wein Lukas Anton , Wurst Klaus , Magauer Thomas
Published: November 2021

Herein, we present our studies to construct seven ent‐trachylobane diterpenoids by employing a bioinspired two‐phase synthetic strategy. The first phase provided enantioselective and scalable access to five ent‐trachylobanes, of which methyl ent‐trachyloban‐19‐oate was produced on a 300 mg scale. During the second phase, chemical C−H oxidation methods were employed to enable selective conversion to two naturally occurring higher functionalized ent‐trachylobanes. The formation of regioisomeric analogs, which are currently inaccessible via enzymatic methods, reveals the potential as well as limitations of established chemical C−H oxidation protocols for complex molecule synthesis.
Thermal and Magnetic Field Switching in a Two‐Step Hysteretic MnIII Spin Crossover Compound Coupled to Symmetry Breakings
Authors: Dobbelaar Emiel , Jakobsen Vibe B. , Trzop Elzbieta , Lee Minseong , Chikara Shalinee , Ding Xiaxin , Müller‐Bunz Helge , Esien Kane , Felton Solveig , Carpenter Michael A. , Collet Eric , Morgan Grace G. , Zapf Vivien S.
Published: November 2021

A MnIII spin crossover complex with atypical two‐step hysteretic thermal switching at 74 K and 84 K shows rich structural–magnetic interplay and magnetic‐field‐induced spin state switching below 14 T with an onset below 5 T. The spin states, structures, and the nature of the phase transitions are elucidated via X‐ray and magnetization measurements. An unusual intermediate phase containing four individual sites, where
are in a pure low spin state, is observed. The splitting of equivalent sites in the high temperature phase into four inequivalent sites is due to a structural reorganization involving a primary and a secondary symmetry‐breaking order parameter that induces a crystal system change from orthorhombic→monoclinic and a cell doubling. Further cooling leads to a reconstructive phase transition and a monoclinic low‐temperature phase with two inequivalent low‐spin sites. The coupling between the order parameters is identified in the framework of Landau theory.
Substrate‐Inspired Fragment Merging and Growing Affords Efficacious LasB Inhibitors
Authors: Kaya Cansu , Walter Isabell , Yahiaoui Samir , Sikandar Asfandyar , Alhayek Alaa , Konstantinović Jelena , Kany Andreas M. , Haupenthal Jörg , Köhnke Jesko , Hartmann Rolf W. , Hirsch Anna K. H.
Published: November 2021

Extracellular virulence factors have emerged as attractive targets in the current antimicrobial resistance crisis. The Gram‐negative pathogen Pseudomonas aeruginosa secretes the virulence factor elastase B (LasB), which plays an important role in the infection process. Here, we report a sub‐micromolar, non‐peptidic, fragment‐like inhibitor of LasB discovered by careful visual inspection of structural data. Inspired by the natural LasB substrate, the original fragment was successfully merged and grown. The optimized inhibitor is accessible via simple chemistry and retained selectivity with a substantial improvement in activity, which can be rationalized by the crystal structure of LasB in complex with the inhibitor. We also demonstrate an improved in vivo efficacy of the optimized hit in Galleria mellonella larvae, highlighting the significance of this class of compounds as promising drug candidates.
An exploration of the population characteristics and behaviours of the white shark in Guadalupe Island, Mexico (2014–2019): Observational data from cage diving vessels
Authors: Santana‐Morales Omar , Zertuche‐Chanes Rebeca , Hoyos‐Padilla Edgar M. , Sepúlveda Chugey , Becerril‐García Edgar E. , Gallo‐Reynoso Juan P. , Barba‐Acuña Isai , Mejía‐Trejo Adán , Aquino‐Baleytó Marc , Sosa‐Nishizaki Oscar , Ketchum James T. , Beas‐Luna Rodrigo
Published: November 2021

In the eastern North Pacific, the Guadalupe Island Biosphere Reserve (GIBR) is one of the most renowned white shark (Carcharodon carcharias) aggregation sites studied to date, and an important tourism activity has been developed in the reserve.

This study used tourist‐based cage diving activities to biologically monitor white sharks from 2014 to 2019 within the GIBR.

The data indicated a gradual increase in the overall abundance of white sharks with an age‐structure shift, as young of the year and juvenile sharks were more prevalent during the latter part of the study period (2016–2019).

The arrival of young of the year and juvenile white sharks coincided with regional changes in oceanographic conditions off California and Baja California.

The arrival of adult female white sharks coincided with the seasonal peak in elephant seal abundance.

Records of high‐risk white shark behaviours, a shift to sharks of younger ages, and the high prevalence of small individuals during cage diving activities supports the need for the continued revision of tourism operational protocols.

This study highlights the importance of white shark biological monitoring to identify threats and challenges to the growing tourism industry and the management of the species in Guadalupe Island and in other aggregation sites.
Ag(I)‐Catalyzed/Acid‐Mediated Cascade Cyclization of ortho‐Alkynylaryl‐1,3‐dicarbonyls to Access Arylnaphthalenelactones and Furanonaphthol Libraries via Aryl‐Disengagement
Authors: Laohapaisan Pavitra , Lumyong Kanyapat , Tummatorn Jumreang , Thongsornkleeb Charnsak , Chatwichien Jaruwan , Supantanapong Nantamon , Ruchirawat Somsak
Published: November 2021

ortho‐Alkynylarylketone derivatives were employed as key precursors for a one‐pot synthesis of arylnaphthalenelactone and furanonaphthol libraries. In this work, we discovered a cost‐effective protocol to prepare arylnaphthalenelactones in one‐pot using inexpensive starting material, malonate ester, which was conveniently functionalized leading to a variety of structures. Moreover, we also found an unexpected oxy‐dearylation reaction which could be used to synthesize furanonaphthol analogs. These novel methods could be applied to a broad range of substrates to give the corresponding products in up to 83% yield. Notably, these classes of compounds exhibited more significant inhibition against protein‐tyrosine phosphatase 1B (PTP1B) enzyme than a standard compound, ursolic acid.
Bilingualism effects in pronoun comprehension: Evidence from children with autism
Authors: Skrimpa Vasileia , Spanou Vasilina , Bongartz Christiane , Peristeri Eleni , Andreou Maria , Papadopoulou Despina
Published: November 2021

The prevalence of autism worldwide has risen steadily in the last two decades, while bilingualism is also becoming increasingly prevalent in today's rapidly globalizing world. The current study aimed to investigate bilingualism effects in the pronoun resolution skills of children with autism in comparison to age‐matched monolingual children with autism, as well as monolingual and bilingual children of typical development (Ν = 20 participants per group). Results showed that autistic children had general difficulty anchoring ambiguous pronouns to entities that were linguistically expressed in discourse, yet, the bilingual children with autism were more sensitive to the topicality of the entities in syntactic subject position and more prone to identify them as suitable referents of ambiguous null pronouns as compared to their monolingual peers. The findings suggest that bilingualism is not detrimental to autistic children's pronoun resolution skills. The current study aimed at determining how bilingualism influences ambiguous pronoun comprehension in children with autism as compared to bilingual and monolingual children of typical development. The findings show that bilingualism was not detrimental to the autistic children's pronoun resolution skills, further suggesting that having acquired more than one language does not exacerbate autistic children's deficits in the comprehension of pronouns.
Comparison of allogeneic hematopoietic stem cell transplantation and TKI combined with chemotherapy for adult philadelphia chromosome positive acute lymphoblastic leukemia: a systematic review and meta‐analysis
Authors: Zeng Qiang , Xiang Bing , Liu Zhigang
Published: November 2021

Objective

This study seeks to clarify whether allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is necessary for adult patients with Philadelphia chromosome‐positive acute lymphoblastic leukemia (Ph+ ALL) in post‐remission based on a comparison with tyrosine kinase inhibitor (TKI) combined with chemotherapy.

Methods

We searched the Pubmed, Embase, and Web of Science databases and limited the date range for the studies from January 2010 to August 2020. A hazard ratio (HR) with a 95% confidence interval (CI) was employed to assess overall survival (OS) and relapse‐free survival (RFS), and an odds ratio (OR) with a 95% CI was used to evaluate the ratio of non‐relapsed mortality (NRM) and non‐relapsed survival (NRS). All analyses were conducted with Stata software 16.0 and Revman 5.3.

Results

Fifteen studies, totaling 959 patients, were included in our analysis. Among those patients, 473 underwent allo‐HSCT, and 486 received TKI plus chemotherapy. The pooled results showed no difference in OS between outcomes for patients receiving TKI plus chemotherapy and those treated with allo‐HSCT (HR = 0.76, 95% CI [0.51–1.12], p = 0.16). Patients undergoing allo‐HSCT did better than those receiving TKI plus chemotherapy regarding RFS (HR = 0.48, 95% CI [0.37–0.63], p = 0.00), and NRS (OR = 2.64, 95% CI [1.25–5.57], p = 0.00). The NRM rate of the TKI plus chemotherapy group was significantly lower than the allo‐HSCT group (OR = 2.33, 95% CI [1.51–3.59], p = 0.00).

Conclusion

TKI combined with chemotherapy can be considered a post‐remission treatment option for adult Ph+ ALL patients who are ineligible for allo‐HSCT. However, more prospective studies with large sample sizes should be carried out in the future.
Workplace COVID‐19 vaccine incentives and the ADA
Authors: Lyerly Eric
Published: November 2021

Most college and university employees have complied with state and institutional vaccine mandates, both within and beyond college athletics. But some have resisted, leading to suspensions or job loss, including the recent firing of Washington State University's head football coach and four assistant coaches.
Selective Capture of Anti‐N‐glucosylated NTHi Adhesin Peptide Antibodies by a Multivalent Dextran Conjugate
Authors: Mazzoleni Antonio , Real‐Fernandez Feliciana , Nuti Francesca , Lanzillo Roberta , Brescia Morra Vincenzo , Dambruoso Paolo , Bertoldo Monica , Rovero Paolo , Mallet Jean‐Maurice , Papini Anna Maria
Published: November 2021

Tentacle‐like polymers decorated with several copies of peptide antigens can be interesting tools for increasing the ability to capture circulating antibodies in patient sera, using cooperative effects for stronger avidity. We previously showed that antibodies from multiple sclerosis (MS) patient sera preferentially recognize hyperglucosylated adhesin protein HMW1ct of non‐typeable Haemophilus influenzae (NTHi). We selected the C‐terminal HMW1ct(1347–1354) minimal epitope and prepared the diglucosylated analogue Ac‐KAN(Glc)VTLN(Glc)TTG‐K(N3)‐NH2 to graft a 40 kDa dextran scaffold modified with glycidyl‐propargyl moieties to perform a copper catalyzed alkyne‐azide coupling reaction (CuAAC). Quantitative NMR measurements allowed the characterization of the peptide loading (19.5 %) on the multivalent dextran conjugate. This novel polymeric structure displayed optimal capturing properties of both IgG and, more interestingly, IgM antibodies in MS sera. Specific antibodies from a representative MS serum, were successfully depleted using a Sepharose resin bearing the new glucosylated multivalent conjugate, as confirmed by ELISA. These results may offer a promising proof‐of‐concept for the selective purification of high affinity autoantibodies from sera of autoimmune patients, in general, and of specific high affinity antibodies against a minimally glcosylated epitope Asn(Glc) from sera of multiple sclerosis (MS) patients, in particular.
Intra‐operative application of ultrasonography (USG) for reduction of zygomatic arch fracture
Authors: Acharya Pradeep , Dongol Ashok , Yadav Anjani Kumar , Bhattarai Nilima , Jaisani Mehul Rajesh
Published: November 2021

Zygomatic arch fractures are the most common facial fractures or second in frequency after the nasal fractures. The high incidence of zygomatic fractures probably relates to its prominent position in the facial skeleton; hence, it is frequently exposed to fractures. This case report presents an left‐sided isolated zygomatic arch fracture after subjected to routine investigations and radiographs like submentovertex and CT scans. The patient was operated under general anesthesia for the reduction of zygomatic arch by Gille's temporal approach with the use of Ultrasound intra‐operatively. Recommendation for the use of ultrasonography in the identification of zygomatic arch fractures intra‐operatively operatively.
On the Supra‐LUMO Interaction: Case Study of a Sudden Change of Electronic Structure as a Functional Emergence
Authors: Gosset Alexis , Lachmanová Štěpánka Nováková , Cherraben Sawsen , Bertho Gildas , Forté Jérémy , Perruchot Christian , de Rouville Henri‐Pierre Jacquot , Pospíšil Lubomír , Hromadová Magdaléna , Brémond Éric , Lainé Philippe P.
Published: November 2021

The synergistic functioning of redox‐active components that emerges from prototypical 2,2′‐di(N‐methylpyrid‐4‐ylium)‐1,1′‐biphenyl is described. Interestingly, even if a trans conformation of the native assembly is expected, due to electrostatic repulsion between cationic pyridinium units, we demonstrate that cis conformation is equally energy‐stabilized on account of a peculiar LUMO (SupLUMO) that develops through space, encompassing the two pyridiniums in a single, made‐in‐one‐piece, electronic entity (superelectrophoric behavior). This SupLUMO emergence, with the cis species as superelectrophore embodiment, originates in a sudden change of electronic structure. This finding is substantiated by insights from solid state (single‐crystal X‐ray diffraction) and solution (NOE NMR and UV‐vis‐NIR spectroelectrochemistry) studies, combined with electronic structure computations. Electrochemistry shows that electron transfers are so strongly correlated that two‐electron reduction manifests itself as a single‐step process with a large potential inversion consistent with inner creation of a carbon‐carbon bond (digital simulation). Besides, absence of reductive formation of dimers is a further indication of a preferential intramolecular reactivity determined by the SupLUMO interaction (cis isomer pre‐organization). The redox‐gated covalent bond, serving as electron reservoir, was studied via atropisomerism of the reduction product (VT NMR study). The overall picture derived from this in‐depth study of 2,2′‐di(N‐methylpyrid‐4‐ylium)‐1,1′‐biphenyl proves that trans and cis species are worth considered as intrinsically sharply different, that is, as doubly‐electrophoric and singly‐superelectrophoric switchable assemblies, beyond conformational isomerism. Most importantly, the through‐space‐mediated SupLUMO may come in complement of other weak interactions encountered in Supramolecular Chemistry as a tool for the design of electroactive architectures.
Electroreductive Cross‐Coupling of Trifluoromethyl Alkenes and Redox Active Esters for the Synthesis of Gem‐Difluoroalkenes
Authors: Claraz Aurélie , Allain Clémence , Masson Géraldine
Published: November 2021

An electroreductive access to gem‐difluoroalkenes has been developed through the decarboxylative/defluorinative coupling of N‐hydroxyphtalimides esters and α‐trifluoromethyl alkenes. The electrolysis is performed under very simple reaction conditions in an undivided cell using cheap carbon graphite electrodes. This metal‐free transformation features broad scope with good to excellent yields. Tertiary, secondary as well as primary alkyl radicals could be easily introduced. α‐aminoacids L‐aspartic and L‐glutamic acid‐derived redox active esters were good reactive partners furnishing potentially relevant gem‐difluoroalkenes. In addition, it has been demonstrated that our electrosynthetic approach toward the synthesis of gem‐difluoroalkenes could use an easily prepared Kratitsky salt as alkyl radical precursor via a deaminative/defluorinative carbofunctionalization of trifluoromethylstyrene.
A Phosphorus‐Based Pacman Dication Generated by Cooperative Self‐Activation of a Pacman Phosphane
Authors: Eickhoff Liesa , Ohms Leon , Bresien Jonas , Villinger Alexander , Michalik Dirk , Schulz Axel
Published: November 2021

Formal coordination of phosphorus(III) by a calix[4]pyrrole Schiff base ligand was achieved through the reaction of this ligand with PCl3 under basic conditions. The reaction product adopts a Pacman conformation with two P−Cl moieties, one in exo and one in endo position. It represents the first non‐metal compound of calix[4]pyrrole Schiff base ligands and of Pacman ligands in general. The spatial neighborhood of the two phosphorus atoms enables cooperative reactions. As a first example, the chloride abstraction with AgOTf is presented, yielding a macrocyclic dication with two embedded phosphorus(III) monocations, which both undergo a cooperative, internal activation reaction with an adjacent C=N double bond. This intramolecular redox process affords two pentacoordinated phosphorus(V) centers within the Pacman dication. All reaction products were fully characterized and all results are supported by computations.
1‐[2‐(1‐Cyclobutylpiperidin‐4‐yloxy)‐6,7‐dihydro‐4H‐thiazolo[5,4‐c]pyridin‐5‐yl]propan‐1‐one: a Histamine H3 Receptor Inverse Agonist with Efficacy in Animal Models of Cognition
Authors: Shinde Anil Karbhari , Badange Rajesh Kumar , Reballi Veena , Achanta Pramod Kumar , Bojja Kumar , Manchineella Sravanthi , Rao Muddana Nageswara , Subramanian Ramkumar , Choudary Palacharla Raghava , Benade Vijay , Jayarajan Pradeep , Thentu Jagadeesh Babu , Lingavarapu Bujji Babu , Yarra Sivasekhar , Kagita Narendra , Rao Doguparthi Mallikarjuna , Mohammed Abdul Rasheed , Nirogi Ramakrishna
Published: November 2021

A series of chemical optimizations, which was guided by in vitro affinity at histamine H3 receptor (H3R), modulation of lipophilicity, ADME properties and preclinical efficacy resulted in the identification of 1‐[2‐(1‐cyclobutylpiperidin‐4‐yloxy)‐6,7‐dihydro‐4H‐thiazolo[5,4‐c]pyridin‐5‐yl]propan‐1‐one (45 e) as a potent and selective (Ki=4.0 nM) H3R inverse agonist. Dipsogenia induced by (R)‐α‐methylhistamine was dose dependently antagonized by 45 e, confirming its functional antagonism at H3R. It is devoid of hERG and phospholipidosis issues. Compound 45 e has adequate oral exposures and favorable half‐life in both rats and dogs. It has demonstrated high receptor occupancy (ED80=0.22 mg/kg) and robust efficacy in object recognition task and, dose dependently increased acetylcholine levels in brain. The sub‐therapeutic doses of 45 e in combination with donepezil significantly increased acetylcholine levels. The potent affinity, selectivity, in vivo efficacy and drug like properties together with safety, warrant for further development of this molecule for potential treatment of cognitive disorders associated with Alzheimer's disease.
Transoral robotic surgery adoption and safety in treatment of oropharyngeal cancers
Authors: Oliver Jamie R. , Persky Michael J. , Wang Binhuan , Duvvuri Umamaheswar , Gross Neil D. , Vaezi Alec E. , Morris Luc G. T. , Givi Babak
Published: November 2021

Background

Transoral robotic surgery (TORS) was approved by the Food and Drug Administration in 2009 for the treatment of oropharyngeal cancers (oropharyngeal squamous cell carcinoma [OPSCC]). This study investigated the adoption and safety of TORS.

Methods

All patients who underwent TORS for OPSCC in the National Cancer Data Base from 2010 to 2016 were selected. Trends in the positive margin rate (PMR), 30‐day unplanned readmission, and early postoperative mortality were evaluated. Outcomes after TORS, nonrobotic surgery (NRS), and nonsurgical treatment were compared with matched‐pair survival analyses.

Results

From 2010 to 2016, among 73,661 patients with OPSCC, 50,643 were treated nonsurgically, 18,024 were treated with NRS, and 4994 were treated with TORS. TORS utilization increased every year from 2010 (n = 363; 4.2%) to 2016 (n = 994; 8.3%). The TORS PMR for base of tongue malignancies decreased significantly over the study period (21.6% in 2010‐2011 vs 15.8% in 2015‐2016; P = .03). The TORS PMR at high‐volume centers (≥10 cases per year; 11.2%) was almost half that of low‐volume centers (<10 cases per year; 19.3%; P < .001). The rates of 30‐day unplanned readmission (4.1%) and 30‐day postoperative mortality (1.0%) after TORS were low and did not vary over time. High‐volume TORS centers had significantly lower rates of 30‐day postoperative mortality than low‐volume centers (0.5% vs 1.5%; P = .006). In matched‐pair analyses controlling for clinicopathologic cofactors, 30‐, 60‐, and 90‐day posttreatment mortality did not vary among patients with OPSCC treated with TORS, NRS, or nonsurgical treatment.

Conclusions

TORS has become widely adopted and remains safe across the country with a very low risk of severe complications comparable to the risk with NRS. Although safety is excellent nationally, high‐volume TORS centers have superior outcomes with lower rates of positive margins and early postoperative mortality.
Association between metabolic syndrome and its components and incident colorectal cancer in a prospective cohort study
Authors: Tran Tao Thi , Gunathilake Madhawa , Lee Jeonghee , Kim Jeongseon
Published: November 2021

Background

Metabolic syndrome (MetS) has been identified as a contributor to cancer development. However, reports concerning the association between MetS and colorectal cancer (CRC) have been inconsistent. This study investigated whether MetS, its components, and the number of components increase the risk of CRC.

Methods

This was a prospective cohort study of 41,837 participants recruited from August 2002 to December 2014 from the National Cancer Center in South Korea. The participants were followed until December 2017 to identify incident CRC cases. The participants underwent laboratory tests at the baseline. Additionally, a self‐administered questionnaire collected information concerning lifestyle and general characteristics at the baseline. A Cox proportional hazards model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) to explore the association between MetS and its components and CRC risk after adjustments for confounding variables.

Results

In total, 128 incident CRC cases were identified during the follow‐up period. An increased CRC risk was found among participants with MetS (HR, 1.63; 95% CI, 1.08‐2.44). Additionally, elevated blood pressure (HR, 1.50; 95% CI, 1.05‐2.15) and a high fasting glucose level (HR, 1.80; 95% CI, 1.23‐2.63) were associated with an elevated risk of CRC. Notably, an increased risk was identified among participants with abdominal obesity coexisting with another component of MetS.

Conclusions

These results suggest that MetS is a risk factor for CRC. Greater emphasis should be placed on the importance of CRC screening among individuals with abdominal obesity coexisting with another component of MetS.

Lay Summary

Colorectal cancer (CRC) ranks as the third most common cancer type in terms of incidence.

Metabolic syndrome (MetS) has been identified as a contributor to cancer development.

However, the association between MetS and CRC remains controversial because of a lack of consistent findings in previous studies.

In this study, the National Cholesterol Education Program's Adult Treatment Panel III guidelines are used for the diagnosis of MetS.

MetS is found to be a predictor of CRC. Additionally, the importance of CRC screening among individuals with 2 components of MetS should be emphasized.
A New Comprehensive Approach to Assess the Probability of Success of Development Programs Before Pivotal Trials
Authors: Hampson Lisa V. , Holzhauer Björn , Bornkamp Björn , Kahn Joseph , Lange Markus R. , Luo Wen‐Lin , Singh Pritibha , Ballerstedt Steffen , Cioppa Giovanni Della
Published: November 2021

The point at which clinical development programs transition from early phase to pivotal trials is a critical milestone. Substantial uncertainty about the outcome of pivotal trials may remain even after seeing positive early phase data, and companies may need to make difficult prioritization decisions for their portfolio. The probability of success (PoS) of a program, a single number expressed as a percentage reflecting the multitude of risks that may influence the final program outcome, is a key decision‐making tool. Despite its importance, companies often rely on crude industry benchmarks that may be “adjusted” by experts based on undocumented criteria and which are typically misaligned with the definition of success used to drive commercial forecasts, leading to overly optimistic expected net present value calculations. We developed a new framework to assess the PoS of a program before pivotal trials begin. Our definition of success encompasses the successful outcome of pivotal trials, regulatory approval and meeting the requirements for market access as outlined in the target product profile. The proposed approach is organized in four steps and uses an innovative Bayesian approach to synthesize all relevant evidence. The new PoS framework is systematic and transparent. It will help organizations to make more informed decisions. In this paper, we outline the rationale and elaborate on the structure of the proposed framework, provide examples, and discuss the benefits and challenges associated with its adoption.
Long‐Term Preservation of Short‐Lived Photoproducts of Phytochromes at Room Temperature
Authors: Köhler Lisa , Gärtner Wolfgang , Matysik Jörg , Song Chen
Published: November 2021

Phytochromes (Phys) are biliproteins that regulate light responses in plants, fungi, and microorganisms through photoconversion between a dark state and a photoproduct. Thermal reversion of the photoproduct is an intrinsic property of all Phys, typically occurring on a timescale of seconds to days. Despite methodological advances, the structural and spectroscopic determination of short‐lived photoproducts has proven challenging. We herein present an innovative approach for photoproduct stabilisation by incorporating the protein into trehalose glasses (TGs). The resulting Phy–trehalose matrices were investigated by UV/Vis absorption and solid‐state NMR spectroscopies. Our results demonstrate that the TGs strongly inhibit thermal reversion of the incorporated Phy proteins for periods as long as several weeks at room temperature (RT), during which the proteins fully sustain their native structures and spectral and biochemical properties. This sample preparation approach is beneficial for revealing bona fide structure/function relationships of short‐lived photoproducts that are otherwise not accessible, thus paving the way towards a deeper molecular understanding of the diversified spectral properties of Phys. Our results also provide new insights into the molecular mechanism of trehalose bioprotection.
Ligand‐Free Copper‐Catalyzed Ullmann‐Type C−O Bond Formation in Non‐Innocent Deep Eutectic Solvents under Aerobic Conditions
Authors: Quivelli Andrea Francesca , Marinò Manuela , Vitale Paola , García‐Álvarez Joaquín , Perna Filippo M. , Capriati Vito
Published: November 2021

An efficient and novel protocol was developed for a Cu‐catalyzed Ullmann‐type aryl alkyl ether synthesis by reacting various (hetero)aryl halides (Cl, Br, I) with alcohols as active components of environmentally benign choline chloride‐based eutectic mixtures. Under optimized conditions, the reaction proceeded under mild conditions (80 °C) in air, in the absence of additional ligands, with a catalyst [CuI or CuII species] loading up to 5 mol% and K2CO3 as the base, providing the desired aryloxy derivatives in up to 98 % yield. The potential application of the methodology was demonstrated in the valorization of cheap, easily available, and naturally occurring polyols (e. g., glycerol) for the synthesis of some pharmacologically active aryloxypropanediols (Guaiphenesin, Mephenesin, and Chlorphenesin) on a 2 g scale in 70–96 % yield. Catalyst, base, and deep eutectic solvent could easily and successfully be recycled up to seven times with an E‐factor as low as 5.76.
Brevis factorρto evaluate data aggregation tree scheduling heuristics in sensor networks
Authors: Kale Preeti A. , Nene Manisha J.
Published: November 2021

In Sensor Networks (SNs), Network Lifetime (NL) enhancement using Data Aggregation Trees (DATs) is an extensively studied NP complete problem. The study in this paper investigates the existing DAT scheduling heuristics and proposes a metric termed asBrevis Factor ρto evaluate the merit of the employed heuristics. Then, theρmetric is applied to the state‐of‐art DAT scheduling heuristics which are typically based on Residual Energy (RE) parameter of the sensor nodes. Further, this paper proposes a new heuristics parameter for DAT scheduling based on the Number of Neighboring nodes (NN). Performance of NN‐based heuristics is evaluated with rigorous simulations, and the results demonstrate improvement in NL as compared with the state‐of‐art. The values ofρare observed for the existing RE‐based heuristics as well as the proposed NN‐based heuristics. The results demonstrate howρmetric values evaluate the DAT scheduling heuristics. In addition, the results facilitate to understand the trade‐off associated with the overheads to reconstruct DATs while improving NL.
Intraspecific interactions in a high‐density leopard population
Authors: Rouse Sarah , Behnoud Pouyan , Hobeali Kaveh , Moghadas Peyman , Salahshour Zolfaghar , Eslahi Hossein , Ommatmohammadi Mousa , Khani Ali , Shabani Abolfazl , Macdonald David W. , Farhadinia Mohammad S.
Published: November 2021

Although less studied than interspecific interactions, interactions among members of the same species can influence space use and temporal activity. Using techniques commonly applied to the analysis of interspecific interactions—multispecies occupancy modeling and the analysis of temporal activity patterns—we studied intraspecific interactions within a high‐density population of Persian leopards (Panthera pardus saxicolor) in Tandoureh National Park, northeastern Iran. Using camera‐trap data, we investigated spatiotemporal interactions between male leopards, lone female leopards, and families (cubs/females with cubs). While we hypothesized that male and female leopards would display different temporal activity patterns, we did not predict spatial avoidance between these groups. We also predicted that leopard families would exhibit spatiotemporal avoidance from male leopards due to the risk of infanticide. Contrary to our expectations, we did not find any evidence for spatial or temporal avoidance between leopard families and adult male leopards. Male and lone female leopards exhibited positive pairwise co‐occurrence, consistent with reports of high overlap between male and female leopard home ranges. While a high level of overlap in temporal activity patterns was found between males/lone females and males/families, there was evidence for variation in the proportion of time each leopard group was active in particular periods of the diel cycle. Male leopards showed cathemeral activity, while lone females and families were more active during daylight hours. The application of these techniques to interactions within a species has improved understanding of the ecology and behavior of this endangered solitary carnivore.
Longitudinal pattern of resource utilization by aquatic consumers along a disturbed subtropical urban river: Estimating the relative contribution of resources with stable isotope analysis
Authors: Wang Sai , Wang Tuan‐Tuan , Xia Wen‐Tong , Chen Zhong‐Bing , Stewart Simon D. , Yang Feng‐Juan , Cheng Gong , Wang Xiao‐Di , Wang Ding‐Ying , Xie Song‐Guang
Published: November 2021

The utilization of food resources by aquatic consumers reflects the structure and functioning of river food webs. In lotic water systems, where food availability and predator–prey relationships vary with gradient changes in physical conditions, understanding diet assimilation by local communities is important for ecosystem conservation. In the subtropical Liuxi River, southern China, the relative contribution of basal resources to the diet assimilation of functional feeding groups (FFGs) was determined by stable carbon (13C) and nitrogen (15N) isotope analyses. The output of Bayesian mixing models showed that diatom‐dominated periphyton (epilithic biofilm), aquatic C3 plants (submerged hydrophytes), and suspended particulate organic matter (SPOM) associated with terrestrial C3 plants contributed the most to the diet assimilation of FFGs in the upper, middle, and lower reaches, respectively. The relative contribution of consumer diet assimilation was weighted by the biomass (wet weight, g/m2) of each FFG to reflect resource utilization at the assemblage level. From the upper to the lower reaches, the spatial variation in the diet assimilation of fish and invertebrate assemblages could be summarized as a longitudinal decrease in periphyton (from 57%–76% to <3%) and an increase in SPOM (from <7% to 51%–68%) with a notable midstream increase in aquatic C3 plants (23%–48%). These results indicate that instream consumers in the Liuxi River rely more on autochthonous production (e.g., periphyton and submerged hydrophytes) than on terrestrially derived allochthonous matter (e.g., terrestrial plants). The pattern of resource utilization by consumers in the mid‐upper Liuxi River is consistent with findings from other open subtropical and neotropical rivers and provides evidence for the riverine productivity model. Our study indicates that protecting inherent producers in rivers (e.g., periphyton and submerged hydrophytes) and restoring their associated habitats (e.g., riffles with cobble substrate) are conducive to aquatic ecosystem management.
Advanced roe deer (Capreolus capreolus) parturition date in response to climate change
Authors: Hagen Robert , Ortmann Sylvia , Elliger Andreas , Arnold Janosch
Published: November 2021

In temperate habitats, the vegetation onset in spring affects the life cycle activities of large herbivores. For one species of large herbivore, roe deer (Capreolus capreolus), parturition is tied to peak resource availability. However, recent long‐term studies of the parturition date of roe deer found only limited support for its earlier occurrence with an earlier onset of spring. In this study, data from a long‐term project (1973–2019) in southern Germany (Baden‐Württemberg; elevation 101–1036 m; 16,130 tagged roe deer fawns) were used to investigate whether the advance in the roe deer parturition date reflected different environmental conditions and was thus explained by temporal and spatial factors. Our results showed a consistent advance toward an earlier parturition date (between 0.16 and 0.33 d/yr), especially for elevations above 750 m, that coincided with an advance in plant phenology. Up to 37% of the variance of the detrended time series of the mean annual parturition was accounted for by the detrended time series of the flowering date of forsythia. Our results suggest a plasticity that allows roe deer to cope with climate‐induced changes along environmental gradients.
Synthesis and Reactivity of a Lewis‐Base‐Stabilized tert‐Butyl Arsanylborane: A Versatile Building Block for Arsenic‐Boron Oligomers
Authors: Lehnfeld Felix , Seidl Michael , Timoshkin Alexey Y. , Scheer Manfred
Published: November 2021

The synthesis and reactivity of the tert‐butyl‐substituted arsanylborane tBuAsHBH2 ⋅ NMe3 (1) stabilized by a Lewis base (LB) are reported. Compound 1 is obtained by the reaction of in situ generated NatBuAsH with IBH2 ⋅ NMe3. By the reaction of 1 with Lewis acids the neutral compounds BBr3 ⋅ tBuAsHBH2 ⋅ NMe3 (2) and BH3 ⋅ tBuAsHBH2 ⋅ NMe3 (3) as well as coordination products towards Group 6 metal complexes [M(CO)4(tBuAsHBH2 ⋅ NMe3)2] (M=Cr, Mo, W; 4 a–c) are obtained. Upon reaction with IBH2 ⋅ LB (LB=SMe2, NMe3), the cationic oligomeric arsanylboranes [(Me3N ⋅ BH2tBuAsHBH2 ⋅ NMe3)]I (5) and [H2B(tBuAsHBH2 ⋅ NMe3)2]I (6) were isolated. Compound 1 was also used as starting material for the synthesis of the first oligomeric arsanylboranes obtained by thermal oligomerization under different conditions. DFT computations support the experimental observations.
Nature of C−I⋅⋅⋅π Halogen Bonding and its Role in Organocatalysis
Authors: Portela Susana , Fernández Israel
Published: November 2021

The nature of the C−I⋅⋅⋅π halogen bonding and its mode of activation in organocatalysis have been quantitatively explored in detail by means of Density Functional Theory (DFT) calculations. To this end, the uncatalyzed homo‐[4+2]‐cycloaddition reaction involving 2‐alkenylindoles is compared to the analogous process mediated by iodine‐substituted azolium salts. It is found that the catalysts establish relatively strong C−I⋅⋅⋅π noncovalent interactions with the indole reactant, which are characterized by a high degree of covalency. This interaction results in a significant acceleration of the cycloaddition by lowering the activation barrier up to 6 kcal/mol with respect to the uncatalyzed reaction. The calculations predict that this barrier can be further reduced by increasing the electrophilicity of the catalyst. Our quantitative analyses reveal that the origin of the catalysis is found mainly in a significant reduction of the steric (Pauli) repulsion between the diene and dienophile, therefore confirming the generality of the recently introduced Pauli‐repulsion lowering concept.
Seed: Gendered Vernaculars and Relational Possibilities
Authors: Chapman Susannah , Chacko Xan Sarah
Published: November 2021

This contribution to feminist vocabulary provides a genealogy of the term seed. We both work on practices of care and control related to seeds, from seed banking and agricultural development projects to everyday practices of keeping, saving, and tinkering with seeds. As a term, seed evokes gendered ideas about human reproduction that center masculinity and virility, even though the botanical seeds are in fact already‐fertilized embryos. This entry takes up the gendered dimension of seeds (and the elisions it produces) as a lens to interrogate ideas of use, usefulness, and uselessness (Ahmed 2019) in the world of biodiversity banking and plant genetic resources. With examples from seed banking and farming in West Africa, and with inspiration from feminist philosophers and anthropologists Sylvia Wynter, Marilyn Strathern, and Sara Ahmed, this provocation contributes to the vocabularies of feminist anthropology and science studies. Since the stories we tell about the world are filled with metaphor, why not complicate the vernacular understanding and usage of seed to reflect the queer and matrilineal possibilities that we see all around us, instead of the potent patrilineality that remains as a vestigial reminder of the values we would rather leave behind?
Alcohol consumption among older adults: Findings from the ELSI‐Brazil study
Authors: Paula Tassiane C. S. , Chagas Camila , Henrique Amanda E. G. , Castro‐Costa Erico , Lima‐Costa Maria Fernanda , Ferri Cleusa P.
Published: November 2021

Objectives

This study estimates the national prevalence of drinking patterns (current, heavy, and binge) and the associated factors, among older Brazilians.

Design

Cross‐sectional study using survey data from ELSI‐Brazil (2015–2016).

Setting/Participants

A total of 7839 adults aged 50 years or older.

Measurements

Respondents were asked about alcohol drinking. Alcohol consumption status was categorized as current drinkers (last month), heavy drinkers (≥7 drinks/week for females and ≥14 drinks/week for males), and binge drinkers (≥4 drinks on one occasion for females and ≥5 drinks on one occasion for males). Covariates included sociodemographic characteristics, tobacco smoking, depression, and number of chronic diseases.

Results

Of the 7839 participants, 29.4% were current drinkers, 5.1% were heavy drinkers, and 10.3% reported binge drinking. In the ≥60 years old age group, the prevalence of current drinking was 23.8%, 3.9% were heavy drinkers, and 6.7% reported binge drinking. All drinking patterns had similar associated factors: being male, being younger, having higher education, tobacco smoking, and falls. In addition, the greater the number of chronic conditions, the lower the prevalence of current drinking and binge drinking.

Conclusion

Heavy drinking and binge drinking are often reported by older Brazilians, particularly among males, those with higher education and in the younger age groups. These behaviors can negatively affect the health of older adults. It is, therefore, important to identify the problems related to alcohol consumption among older adults to minimize the risks and harms.
Not just about machines: Analysis of MRI quality determinants in the Turkish health system context
Authors: Özen İlhan Can , Başar Dilek , Öztürk Selcen , Gümeler Ekim , Akata Deniz , Çiftçi Arbay Özden
Published: November 2021

This study aims to investigate the determinants of the quality MRI in the Turkish healthcare system. The analysis is done by analysing the referred cases to a major university radiology department in Turkey, and matching the hospital and MRI use characteristics of the source institutions, where the original MRI was taken. Quality of MRI was measured by specialist radiologists. The resulting quality was analysed by gender and imaging area characteristics, source institutional quality, MRI use statistics in source institution and MRI machine use inclination of the source institution. Chi‐square and logistic regression were conducted, with regional fixed effects. In the largest dataset, the highest quality institutions have significantly higher average expected MRI quality compared to one level beneath them (0.74 vs. 0.63) (P = 0.02), there is also a significant MRI quality difference between the second highest level of institution, and the third and the fourth (0.63–0.54). Smaller (<0.1) but significant quality difference (P = 0.05) exists for institutions with the lowest two quality levels. In the smaller dataset, with data only from the lowest two institutional quality groups, with a finer institutional quality grading, differences in institutional quality is again found to be a significant driver of MRI quality (P = 0.035).
Consequences and implications of the coronavirus disease (COVID‐19) on pregnancy and newborns: A comprehensive systematic review and meta‐analysis
Authors: de Medeiros Kleyton S. , Sarmento Ayane C. A. , Costa Ana P. F. , Macêdo Luíza T. de A. , da Silva Luís A. S. , de Freitas Cijara L. , Simões Ana C. Z. , Gonçalves Ana K.
Published: November 2021

Background

Pregnant patients are potentially vulnerable to COVID‐19.

Objectives

To clarify the clinical features of COVID‐19 and analyze maternal/fetal morbidity and mortality and the obstetric and neonatal outcomes of pregnant patients.

Search strategy

Embase, PubMed, Web of Science, CINAHAL, LILACS, Google Scholar, and Scopus.

Selection criteria

Articles published from December 2019 to February 2021.

Data collection and analysis

The reviewers extracted relevant data from the full‐text. Data synthesis was performed using the R‐4.1.0 Project for Statistical Computing for Windows. The meta‐analysis of the included studies was carried out using the random‐effects model (DerSimonian and Laird). Heterogeneity was measured using I2 analysis.

Results

A total of 70 studies included 10 047 pregnant women with COVID‐19, of whom 71.6% were in their third trimester. The most common symptoms were fever, cough, chest pain, dyspnea, and fatigue. Most newborns were delivered preterm (24%, 95% confidence interval [CI] 0.17–0.34, I2 = 93%) and via cesarean delivery (42%, 95% CI 0.38–0.47, I2 = 92%). There were 108 maternal mortalities (2%, 95% CI 0.01–0.03, I2 = 54%) and 50 abortions (5%, 95% CI 0.03–0.09, I2 = 73%). The neonatal outcomes included fetal distress (11%, 95% CI 0.06–0.19, I2 = 91%), birth weight (15%, 95% CI 0.10–0.21, I2 = 76%), APGAR <7 (19%, 95% CI 0.12–0.28, I2 = 43%), admission to the neonatal intensive care unit (28%, 95% CI 0.17–0.43, I2 = 90%), and fetal mortality (2%, 95% CI 0.01–0.03, I2 = 46%).

Conclusion

 There was no evidence of severe acute respiratory syndrome coronavirus‐2 in the placenta, breast milk, umbilical cord, and amniotic fluid of pregnant patients.

PROSPERO registration number: CRD42020181519.