bluuebunny/crossref_metadata_2025 huggingface dataset:
Docetaxel in combination with metformin enhances antitumour efficacy in metastatic breast carcinoma models: a promising cancer targeting based on PEGylated liposomes
Authors: Vakili-Ghartavol Roghayyeh , Mehrabian Amin , Mirzavi Farshad , Rezayat Seyed Mahdi , Mashreghi Mohammad , Farhoudi Leila , Kharrazi Sharmin , Sadri Kayvan , Jaafari Mahmoud Reza
Published: July 2022

Objectives

Metformin has been shown to kill cancer stem-like cells in genetically various types of breast carcinoma. With the aim to simultaneously eradicate the bulk population of tumour cells and the rare population of cancer stem-like cells in breast cancer tissues, we used the combination chemotherapy of docetaxel (DTX) with metformin (MET). Furthermore, we introduce an active loading method based on ammonium sulphate 250 mM (SA) for encapsulating docetaxel into liposomes.

Methods

Docetaxel and metformin encapsulated into PEGylated liposomes with two different methods based on remote or passive loading methods, respectively. The size and surface charge of the liposomes were characterized. DTX content in the nanoliposomes was measured by the high-performance liquid chromatography method. The drug release profiles were evaluated in phosphate-buffered dextrose 5% with the pH of 6.5 and 7.4. We examined the antitumour activity of Taxotere (TAX), and liposomal formulation of DTX and MET as a monotherapy or combination therapy. The biodistribution of liposomes was also investigated using 99mTc hexamethyl propylene amine oxime method in BALB/c mice bearing 4T1 breast carcinoma tumours.

Key findings

The final formulations were prepared according to the best physicochemical characteristics which were HSPC/mPEG2000-DSPE/Chol (DTX liposomes) and HSPC/DPPG/mPEG2000-DSPE/Chol (MET liposomes), at molar ratios of 85/5/10 and (55/5/5/35), respectively. In vivo experiments showed that when free or liposomal metformin used in combination with liposomal docetaxel, they prolonged median survival time (MST) from 31 in the control group to 46 days, which demonstrates their promising effects on the survival of the 4T1 breast carcinoma mice models. Moreover, combination therapies could significantly increase life span in comparison with phosphate-buffered saline (PBS) and Taxotere groups at the same dose. Furthermore, in the combination therapy study, treatment with DTX liposomes prepared by ammonium sulphate 250 mM buffer alone resulted in similar therapeutic efficacy to combination therapy. The biodistribution study exhibited significant accumulation of DTX liposomes in the tumours due to the Enhanced Permeability and Retention effect.

Conclusions

This study also showed that metformin-based combinatorial chemotherapies have superior efficacy versus their corresponding monotherapy counterparts at same doses. The findings confirm that liposomes based on ammonium sulphate 250 mM could be as a promising formulation for efficient DTX delivering and cancer targeting and therefore merit further investigations.
Bias and representativeness in digitized newspaper collections: Introducing the environmental scan
Authors: Beelen Kaspar , Lawrence Jon , Wilson Daniel C S , Beavan David
Published: July 2022

This article introduces the ‘Environmental Scan’ as answer to the question of hidden biases in digital heritage collections. Its substantive focus is digitized nineteenth-century British provincial newspapers, and in particular the JISC corpus, a popular, publicly-funded resource for scholars. While multiple papers have meticulously investigated the genesis of such newspaper collections, in the process highlighting the often unacknowledged politics of collection, preservation and dissemination via microfilm and now digitization, our aim is to explore questions of representativeness and bias in new ways by enriching computational analysis of digital corpora with the historical insights that can be derived from a contemporaneous reference source: namely, the Victorian newspaper press directories.
Use of MEDEVAC Resources in Austere Settings: Paget–Schroetter in the Deployed Environment
Authors: O’Donnell Mary T , Huang Michelle L , Gerling Kimberely A , Rasmussen Todd E , White Joseph M , Koelling Erin E
Published: July 2022

Medical evacuation (MEDEVAC) from a combat zone requires complex decision-making and coordination of assets. A MEDEVAC helicopter team transports not only battle-injured patients but also patients with urgent non-battle-related medical diagnoses from extremely remote locations and are at the mercy of terrain, weather, and enemy contact. The military represents a young population particularly susceptible to venous thoracic outlet syndrome (vTOS) given the rigorous physical activity demands. Current literature supports immediate anticoagulation and surgical decompression within 14 days of diagnosis of vTOS to prevent long-term morbidity. Presented is a case of service member with vTOS presenting at an extremely remote military clinic who underwent a prompt evacuation ∼7,000 miles utilizing rotary-wing transport, followed by three to four more fixed-wing flights to a military treatment facility in the United States. Immediate recognition and ultrasound of this patient to confirm vTOS upon presentation and effective communication to non-medical military commanders and the receiving medical personnel at each Echelon was necessary to ensure an expedited evacuation. The surgeons treating this patient recommend prompt evacuation of deployed service members with suspected vTOS, venogram at the Role 3 if ultrasound is inconclusive, anticoagulation, and return to a Role 4 CONUS facility for definitive surgical management within 14 days. This case is an example of the efficiency of the military MEDEVAC system on a global scale, ensuring optimum medical care for all service members deployed.
Madurella mycetomatis grains within a eumycetoma lesion are clonal
Authors: Nyuykonge Bertrand , Siddig Emmanuel Edwar , Konings Mickey , Bakhiet Sahar , Verbon Annelies , Klaassen Corné H W , Fahal Ahmed Hassan , van de Sande Wendy W J
Published: July 2022

Eumycetoma is a neglected tropical infection of the subcutaneous tissue, characterized by tumor-like lesions and most commonly caused by the fungus Madurella mycetomatis. In the tissue, M. mycetomatis organizes itself in grains, and within a single lesion, thousands of grains can be present. The current hypothesis is that all these grains originate from a single causative agent, however, this hypothesis was never proven. Here, we used our recently developed MmySTR assay, a highly discriminative typing method, to determine the genotypes of multiple grains within a single lesion. Multiple grains from surgical lesions obtained from 11 patients were isolated and genotyped using the MmySTR panel. Within a single lesion, all tested grains shared the same genotype. Only in one single grain from one patient, a difference of one repeat unit in one MmySTR marker was noted relative to the other grains from that patient. We conclude that within these lesions the grains originate from a single clone and that the inherent unstable nature of the microsatellite markers may lead to small genotypic differences.

Lay Abstract

In lesions of the implantation mycosis mycetoma many Madurella mycetomatis grains are noted. It was unknown if grains arose after implantation of a single isolate or a mixture of genetically diverse isolates. By typing the mycetoma grains we showed that all grains within a single lesion were clonal and originated from a single isolate.
Investigating the X-ray polarization of lamp-post coronae in BHXRBs
Authors: Zhang Wenda , Dovčiak Michal , Bursa Michal , Karas Vladimír , Matt Giorgio , Ursini Francesco
Published: July 2022

High-sensitivity X-ray polarimetric observations of black hole X-ray binaries, which will soon become available with the launches of space-borne X-ray observatories with sensitive X-ray polarimeters, will be able to put independent constraints on the black hole as well as the accretion flow, and possibly break degeneracies that cannot be resolved by spectral/timing observations alone. In this work, we perform a series of general relativistic Monte Carlo radiative transfer simulations to study the expected polarization properties of X-ray radiation emerging from lamp-post coronae in black hole X-ray binaries. We find that the polarization degree of the coronal emission of black hole X-ray binaries is sensitive to the spin of the black hole, the height of the corona, and the dynamics of the corona.
High-throughput method for the hybridisation-based targeted enrichment of long genomic fragments for PacBio third-generation sequencing
Authors: Steiert Tim Alexander , Fuß Janina , Juzenas Simonas , Wittig Michael , Hoeppner Marc Patrick , Vollstedt Melanie , Varkalaite Greta , ElAbd Hesham , Brockmann Christian , Görg Siegfried , Gassner Christoph , Forster Michael , Franke Andre
Published: July 2022

Hybridisation-based targeted enrichment is a widely used and well-established technique in high-throughput second-generation short-read sequencing. Despite the high potential to genetically resolve highly repetitive and variable genomic sequences by, for example PacBio third-generation sequencing, targeted enrichment for long fragments has not yet established the same high-throughput due to currently existing complex workflows and technological dependencies. We here describe a scalable targeted enrichment protocol for fragment sizes of >7 kb. For demonstration purposes we developed a custom blood group panel of challenging loci. Test results achieved > 65% on-target rate, good coverage (142.7×) and sufficient coverage evenness for both non-paralogous and paralogous targets, and sufficient non-duplicate read counts (83.5%) per sample for a highly multiplexed enrichment pool of 16 samples. We genotyped the blood groups of nine patients employing highly accurate phased assemblies at an allelic resolution that match reference blood group allele calls determined by SNP array and NGS genotyping. Seven Genome-in-a-Bottle reference samples achieved high recall (96%) and precision (99%) rates. Mendelian error rates were 0.04% and 0.13% for the included Ashkenazim and Han Chinese trios, respectively. In summary, we provide a protocol and first example for accurate targeted long-read sequencing that can be used in a high-throughput fashion.
Impact of the 21-Gene Recurrence Score Assay on Treatment Decisions and Cost in Patients with Node-Positive Breast Cancer: A Multicenter Study in Quebec
Authors: Hassan Saima , Younan Rami , Patocskai Erica , Provencher Louise , Poirier Brigitte , Sideris Luca , Dubé Pierre , Mihalcioiu Catalin , Chabot-Blanchet Malorie , Guertin Marie-Claude , Boileau Jean-François , Robidoux André
Published: July 2022

Background

The 21-gene Breast Recurrence Score (RS) assay, “the assay”, has led to a paradigm shift for patients with hormone receptor-positive, node-negative early breast cancer and is emerging as an important tool to assist physician-patient decisions in foregoing chemotherapy in node-positive patients. We wanted to better understand the impact of the RS assay in node-positive patients upon physician treatment decisions and treatment cost in Quebec, Canada.

Patients and Methods

We conducted a multicenter, prospective observational trial for Estrogen/Progesterone Receptor (ER/PR)- positive, Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer patients with 1-3 positive lymph nodes. Physicians completed a questionnaire indicating treatment choice prior to and post availability of RS results. The primary endpoint was change in the physician’s recommendation for chemotherapy prior to and post assay results. Secondary endpoints included change in physician’s expressed level of confidence, and changes in estimated cost of recommended treatments prior to and post assay results.

Results

For the entire cohort, physician recommendation for chemotherapy was reduced by an absolute 67.1% by knowledge of the RS assay result (P < .0001). Physician recommendation of chemotherapy was decreased by 75.9% for patients RS result <14 (P < .0001); and 67.5% for patients with RS result 14-25 (P < .0001). Changes in treatment recommendations were associated with an overall reduction in cost by 73.7% per patient, and after incorporating the cost of the RS test, a cost benefit of $823 CAN at 6-month follow-up.

Conclusion

Altogether, we established that the assay led to a two-third reduction in the use of chemotherapy, and was a cost-effective approach for hormone receptor-positive, node-positive breast cancer.
Characteristics and outcomes of a Hispanic lupus nephritis cohort from Mexico
Authors: Zavala-Miranda María Fernanda , Perez-Arias Abril Alicia , Márquez-Macedo Sofía E , Comunidad-Bonilla Roque A , Romero-Diaz Juanita , Morales-Buenrostro Luis E , Mejía-Vilet Juan M
Published: July 2022

Objectives

To characterize the clinical presentation and outcomes of LN in a Hispanic cohort from Mexico.

Methods

We studied 440 subjects with systemic lupus erythematosus and biopsy-proven LN followed for >36 months. We obtained demographic, clinical, laboratory, histopathological and treatment variables. All outcomes were analysed by survival analysis and included response to therapy, renal relapses, progression of kidney disease (decline in eGFR ≥ 30%, doubling of serum creatinine, end-stage kidney disease) and patient survival.

Results

The median age of the study cohort was 29 years (IQR 23–37) and 96% were female. The median eGFR at inclusion was 81 mL/min/1.73m2 (IQR 48–118) and 24 h-uPCR was 3.4 g/g (IQR 1.9–5.6). Mixed class LN (III/IV+V) was the most frequently observed (69%). Over a median follow-up of 79 months, complete response rates were 22.3%, 40.5% and 51.6%, at 6, 12 and 24 months, respectively. Renal relapse rates were 32.3% and 50.6% at 3 and 5 years. By 3 and 5 years, 20.7% and 31.4% had decline in eGFR ≥30%, 14.4% and 22.5% doubled their serum creatinine, and 9.1% and 17.7% progressed to ESKD. The factors associated with loss of kidney function were age, eGFR at presentation, the histologic chronicity index in the kidney biopsy, and the type of response to therapy. Patient survival was 98.2% and 97.1% at 3 and 5 years.

Conclusion

Although the response to treatment and patient survival in this Latin American cohort is comparable to that observed in other regions, there is still a high rate of renal relapses and progression to decline in kidney function.
Telemedicine compared to standard face-to-face care for continuous positive airway pressure treatment: real-world Australian experience
Authors: Kosky Christopher , Madeira Neill , Boulton Kate , Hunter Marie-Therese , Ling Ivan , Reynor Ayesha , Sturdy Gavin , Walsh Jennifer , Dhaliwal Satvinder , Singh Bhajan , Eastwood Peter R , McArdle Nigel
Published: July 2022

Study Objectives

We tested a telemedicine model of care to initiate continuous positive airway pressure (CPAP) for patients with obstructive sleep apnea (OSA) living in remote Western Australia.

Methods

A prospective study comparing telemedicine for CPAP initiation in a remote population versus standard face-to-face CPAP initiation in a metropolitan population. The primary outcome was average nightly CPAP use in the final week of a CPAP trial.

Results

A total of 186 participants were allocated to either telemedicine (n = 56) or standard care (n = 130). The average distance from the study center for the telemedicine group was 979 km (±792 km) compared to 19 km (±14 km) for the standard care group. The CPAP trial duration in the standard care group was less than the telemedicine group (37.6 vs 69.9 days, p < .001). CPAP adherence in the telemedicine group was not inferior to standard care (Standard 4.7 ± 0.2 h, Telemedicine 4.7 ± 0.3 h, p = 0.86). No differences were found between groups in residual apnea-hypopnea index, symptom response, sleep specific quality of life at the end of the trial, and continued CPAP use (3–6 months). Participant satisfaction was high in both groups. Total health care costs of the telemedicine model were less than the standard model of care. An estimated A$4538 per participant in travel costs was saved within the telemedicine group by reducing the need to travel to the sleep center for in-person management.

Conclusions

In remote dwelling adults starting CPAP for the treatment of OSA, outcomes using telemedicine were comparable to in-person management in a metropolitan setting,
Unravelling Species Diversity and Pathogenicity of Colletotrichum Associated with Anthracnose on Osmanthus fragrans in Quanjiao, China
Authors: He Jiao , Li De-Wei , Bian Jin-Yue , Zhu Li-Hua , Huang Lin
Published: July 2022

Osmanthus fragrans is a popular ornamental tree species known for its fragrant flowers and is widely cultivated in Asia, Europe, and North America. Anthracnose is a disastrous threat to the growth and development of O. fragrans and has caused significant economic losses. To reveal the potential pathogen diversity of anthracnose, 127 isolates of Colletotrichum were isolated from the symptomatic leaves. Morphological studies and multilocus phylogenetic analyses with the concatenated sequences of the internal transcribed spacer, glyceraldehyde-3-phosphate dehydrogenase, chitin synthase, actin, beta-tubulin, calmodulin, and the intergenic region between Apn2 and Mat1-2-1, as well as a pairwise homoplasy index, test placed the causal fungi as two new species, Colletotrichum anhuiense (two isolates) and C. osmanthicola (12 isolates), and three known taxa, C. fructicola (18 isolates), C. gloeosporioides (62 isolates), and C. karstii (33 isolates). Among them, C. gloeosporioides was the most dominant, and C. anhuiense was occasionally discovered from the host tissues. Pathogenicity tests in vivo on O. fragrans leaves revealed a significant difference in virulence among these species. Of them, C. gloeosporioides, C. osmanthicola, and C. anhuiense were significantly more virulent than C. fructicola and C. karstii, while C. karstii was the least virulent. To our knowledge, this study was the first to report the pathogen diversity of anthracnose on O. fragrans.
Management Reasoning: Empirical Determination of Key Features and a Conceptual Model
Authors: Cook David A. , Stephenson Christopher R. , Gruppen Larry D. , Durning Steven J.
Published: July 2022

Purpose

Management reasoning is a critical yet understudied phenomenon in clinical practice and medical education. The authors sought to empirically identify key features of management reasoning and construct a model describing the management reasoning process.

Method

In November 2020, 4 investigators each reviewed 10 video clips of simulated outpatient physician–patient encounters and used a coding form to document key features and insights related to management reasoning. The team used a constant comparative approach to distill 120 pages of raw observations into an 18-page list of management tasks, processes, and insights. The team then had a series of discussions to iteratively refine these findings into a parsimonious model of management reasoning.

Results

The investigators empirically identified 12 distinct features of management reasoning: contrasting and selection among multiple solutions; prioritization of patient, clinician, and system preferences and constraints; communication and shared decision making; ongoing monitoring and adjustment of the management plan; dynamic interplay among people, systems, and competing priorities; illness-specific knowledge; process knowledge; management scripts; clinician roles as patient teacher and salesperson; clinician–patient relationship; prognostication; and organization of the clinical encounter (sequencing and time management). Management scripts seemed to play a prominent and critical role. The model of management reasoning comprised 4 steps: instantiation of a management script, identifying (multiple) options and beginning to teach the patient, shared decision making, and ongoing monitoring and adjustment. This model also conceives 2 overarching features: that management reasoning is personalized to the patient and that it occurs between individuals rather than exclusively within the clinician’s mind.

Conclusions

Management scripts constitute a key feature of management reasoning, along with teaching patients about viable options, shared decision making, ongoing monitoring and adjustment, and personalization. Management reasoning seems to be constructed and negotiated between individuals rather than exclusively within the clinician.
Current Recommendations for Perioperative Brain Health: A Scoping Review
Authors: Wooding Denise J. , Field Thalia S. , Schwarz Stephan K.W. , MacDonell Su-Yin , Farmer Jaycee , Rajan Shobana , Flexman Alana M.
Published: July 2022

Perioperative complications such as stroke, delirium, and neurocognitive dysfunction are common and responsible for increased morbidity and mortality. Our objective was to characterize and synthesize the contemporary guidelines on perioperative brain health for noncardiac, non-neurologic surgery in a scoping review. We performed a structured search for articles providing recommendations on brain health published between 2016 and 2021 and included the following complications: perioperative stroke and perioperative neurocognitive disorders, the latter of which encompasses postoperative delirium and a spectrum of postoperative cognitive dysfunction. We categorized recommendations by subtopic (stroke, postoperative delirium, postoperative cognitive dysfunction), type (disclosure/ethics/policies, prevention, risk stratification, screening/diagnosis, and management), and pharmacological versus nonpharmacological strategies. We noted country of origin, specialty of the authors, evidence grade (if available), and concordance/discordance between recommendations. Eight publications provided 129 recommendations, originating from the United States (n=5), Europe (n=1), United Kingdom (n=1), and China (n=1). Three publications (37%) applied grading of evidence as follows: Grading of Recommendations, Assessment, Development, and Evaluations (GRADE): A, 30%; B, 36%; C, 30%; D, 4%. We identified 42 instances of concordant recommendations (≥2 publications) on 15 themes, including risk factor identification, risk disclosure, baseline neurocognitive testing, nonpharmacological perioperative neurocognitive disorder prevention, intraoperative monitoring to prevent perioperative neurocognitive disorders, avoidance of benzodiazepines, delaying elective surgery after stroke, and emergency imaging and rapid restoration of cerebral perfusion after perioperative stroke. We identified 19 instances of discordant recommendations on 7 themes, including the use of regional anesthesia and monitoring for perioperative stroke prevention, pharmacological perioperative neurocognitive disorder management, and postoperative stroke screening. We synthesized recommendations for clinical practice and highlighted areas where high-quality evidence is required to inform best practices in perioperative brain health.
Improving 10-year atherosclerotic cardiovascular disease estimation management using a Smartphrase for automated risk screening
Authors: Chappell Anna L.
Published: July 2022

Background:

Cardiovascular disease (CVD) is the most common cause of death in the United States, and 90% of cardiovascular events are preventable. The 2020 American College of Cardiology/American Heart Association Guidelines on the Primary Prevention of Cardiovascular Disease recommends 10-year atherosclerotic cardiovascular disease (ASCVD) risk estimates for 40- to 75-year-old adults with CVD risk indications to decrease the likelihood of cardiovascular events.

Local Problem:

At the project site, the 10-year ASCVD risk estimates were rarely completed by providers. The purpose of this project was to increase 10-year ASCVD risk estimation screening and improve pharmacological therapy for 40- to 75-year-old patients with CVD risk indications.

Methods:

To increase 10-year ASCVD risk estimation screening and improve pharmacological therapy, a multifaceted bundle was created for providers.

Interventions:

Three interventions were initiated: an electronic health record Smartphrase was created to produce automatic 10-year risk scores; laminated paper reminders for the Smartphrase were visible on providers' desks; educational in-services were performed to promote risk score adherence.

Results:

The project aims were achieved with an increase from a 14% completion rate for 10-year ASCVD risk estimation during the preintervention phase to a 98% completion rate at the end of the postintervention phase. Appropriate pharmacological therapy improved from a 64% rate during the preintervention phase to a maximum rate of 79% during postintervention.

Conclusion:

The project was effective at increasing risk estimate completion and improving appropriate pharmacological therapy. There was an increase in provider–patient discussions toward primary prevention for cardiovascular events.
99mTc-Sestamibi Thyroid Scintigraphy in Amiodarone-Induced Thyrotoxicosis
Authors: Wang Ray , Better Nathan , Sivaratnam Dinesh , Westcott James , Forehan Simon , Christie Michael , Pattison David A. , Fourlanos Spiros
Published: July 2022

99mTc-sestamibi thyroid scintigraphy (STS) can aid in differentiating between types 1 and 2 amiodarone-induced thyrotoxicosis (AIT). We present a consecutive case series of 4 men (aged 56–75 years) in whom both 99mTc-STS and thyroid histology were consistent with a diagnosis of type 2 AIT, representing the first reported histopathologic correlation for this diagnostic test. Median amiodarone treatment duration was 26 months (range, 10–39 months), and amiodarone was discontinued a median of 3 months preoperatively (range, 2–4 months) in all 4 cases. 99mTc-STS is a promising functional imaging modality, which has the potential to aid clinicians in the diagnostic workup and treatment of AIT.
John David Barrow. 29 November 1952—26 September 2020
Authors: Ellis George F. R.
Published: July 2022

John Barrow wrote dozens of books and hundreds of papers, including more than 10 papers and one book during his final illness, addressing a grand problem: why is the universe the way it is? What is the fundamental nature of physics, and what are its cosmological outcomes? His most famous book was on the Anthropic Principle with Frank Tipler, and his most significant physics research was on the possibility of a variation of the fundamental constants of physics—which, if true, requires a rejigging of our foundational physics theories. He was an outstanding communicator of science to the public, being asked to lecturer at as varied places as Downing Street and Buckingham Palace. His most important public service was as director of the Millennium Mathematics Project, for which he was awarded the Queen's Anniversary Prize for Educational Achievement by Queen Elizabeth II at Buckingham Palace. He was awarded many other prizes, including the Templeton Prize, the Gold Medal of the Royal Astronomical Society, both the Kelvin Medal and the Dirac Gold Medal of the Institute of Physics and the Faraday Medal of the Royal Society.
Kenneth Wade. 13 October 1932—16 March 2014
Authors: Mingos D. Michael P.
Published: July 2022

Much of Ken Wade's scientific career was devoted to developing and exploiting the chemistries of boron, aluminium, gallium and indium (the Group 13 elements). He made significant contributions to both experimental and theoretical aspects of the subject and was a highly regarded teacher and attentive research supervisor. Ken was a modest and self-critical man who had a rare ability to recognize patterns in large chemical and molecular structure data sets and express the resulting generalizations in the form of simple rules that experimental chemists could appreciate and use to predict new compounds. Ken was fascinated by the structures of cluster compounds that are based on regular polyhedral shapes. Cluster molecules generally contain groups of metal atoms linked by metal–metal bonds and located on one or more spherical shells. Since the 1960s they have attracted the attention of both academic and industrial chemists. Understanding and predicting their three-dimensional shapes raised a significant intellectual challenge for chemists. The clusters also attracted attention because they occupy an intermediate position between co-ordination compounds based on a single metal atom and the parent metal, which has an infinite number of linked metal atoms. This provided chemists with a unique opportunity to explore the evolution of their electronic and chemical properties as the cluster size increases. Ken was the first to recognize the electronic relationships connecting
closo-
,
nido-
,
arachno-
and
hypho
- clusters. These clusters are inter-related by the successive removal of vertices from a regular
closo-
deltahedron, i.e. a polyhedron with all the faces triangular. His ability to connect the structures of these molecules to the number of valence electrons involved in skeletal bonding represented a significant contribution to chemical bonding theories. Ken communicated his conclusions in very clearly written papers and books. This made the complexities of cluster chemistry amenable to many and especially those who did not have a strong background in quantum chemistry. The skeletal electron counting rules, or Wade's Rules, which Ken pioneered, are now very much part of the fabric of modern cluster chemistry and form an important component of modern undergraduate inorganic chemistry courses. Wade's Rules may be applied to main group and transition metal carbonyl clusters as well as clusters containing both main group and transition metal fragments. Besides providing an accessible entry into cluster chemistry for students, the rules have been used creatively by many leading synthetic chemists to discover new classes of compounds.
Exaggerated trans-membrane charge of ammonium transporters in nutrient-poor marine environments
Authors: Kellom Matthew , Pagliara Stefano , Richards Thomas A. , Santoro Alyson E.
Published: July 2022

Transporter proteins are a vital interface between cells and their environment. In nutrient-limited environments, microbes with transporters that are effective at bringing substrates into their cells will gain a competitive advantage over variants with reduced transport function. Microbial ammonium transporters (Amt) bring ammonium into the cytoplasm from the surrounding periplasm space, but diagnosing Amt adaptations to low nutrient environments solely from sequence data has been elusive. Here, we report altered Amt sequence amino acid distribution from deep marine samples compared to variants sampled from shallow water in two important microbial lineages of the marine water column community—Marine Group I Archaea (Thermoproteota) and the uncultivated gammaproteobacterial lineage SAR86. This pattern indicates an evolutionary pressure towards an increasing dipole in Amt for these clades in deep ocean environments and is predicted to generate stronger electric fields facilitating ammonium acquisition. This pattern of increasing dipole charge with depth was not observed in lineages capable of accessing alternative nitrogen sources, including the abundant alphaproteobacterial clade SAR11. We speculate that competition for ammonium in the deep ocean drives transporter sequence evolution. The low concentration of ammonium in the deep ocean is therefore likely due to rapid uptake by Amts concurrent with decreasing nutrient flux.
Visual complexity of egg patterns predicts egg rejection according to Weber's law
Authors: Dixit Tanmay , Apostol Andrei L. , Chen Kuan-Chi , Fulford Anthony J. C. , Town Christopher P. , Spottiswoode Claire N.
Published: July 2022

Visual complexity is ubiquitous in nature. Drivers of complexity include selection in coevolutionary arms races between antagonists. However, the causes and consequences of biological complexity and its perception are largely understudied, partly because complexity is difficult to quantify. Here, we address this by studying egg pattern complexity and its perception in hosts (tawny-flanked prinia
Prinia subflava
), which visually recognize and reject mimetic eggs of their virulent brood parasite (cuckoo finch
Anomalospiza imberbis
). Using field data and an optimization algorithm, we compute a complexity metric which predicts rejection of experimentally placed conspecific eggs in prinia nests. Real cuckoo finch eggs exhibit significantly lower pattern complexity than prinia eggs, suggesting that high complexity benefits hosts because it distinguishes host eggs from parasitic eggs. We show that prinias perceive complexity differences according to Weber's law of proportional processing (i.e. relative, rather than absolute, differences between stimuli are processed in discrimination, such that two eggs with simple patterns are more easily discriminable than two with complex patterns). This may influence coevolutionary trajectories of hosts and parasites. The new methods presented for quantifying complexity and its perception can help us to understand selection pressures driving the evolution of complexity and its consequences for species interactions.
Brain morphology correlates of learning and cognitive flexibility in a fish species (
Poecilia reticulata
)
Authors: Triki Zegni , Granell-Ruiz Maria , Fong Stephanie , Amcoff Mirjam , Kolm Niclas
Published: July 2022

Determining how variation in brain morphology affects cognitive abilities is important to understand inter-individual variation in cognition and, ultimately, cognitive evolution. Yet, despite many decades of research in this area, there is surprisingly little experimental data available from assays that quantify cognitive abilities and brain morphology in the same individuals. Here, we tested female guppies (
Poecilia reticulata
) in two tasks, colour discrimination and reversal learning, to evaluate their learning abilities and cognitive flexibility. We then estimated the size of five brain regions (telencephalon, optic tectum, hypothalamus, cerebellum and dorsal medulla), in addition to relative brain size. We found that optic tectum relative size, in relation to the rest of the brain, correlated positively with discrimination learning performance, while relative telencephalon size correlated positively with reversal learning performance. The other brain measures were not associated with performance in either task. By evaluating how fast learning occurs and how fast an animal adjusts its learning rules to changing conditions, we find support for that different brain regions have distinct functional correlations at the individual level. Importantly, telencephalon size emerges as an important neural correlate of higher executive functions such as cognitive flexibility. This is rare evidence supporting the theory that more neural tissue in key brain regions confers cognitive benefits.
Life-history genotype explains variation in migration activity in Atlantic salmon (
Salmo salar
)
Authors: Niemelä Petri T. , Klemme Ines , Karvonen Anssi , Hyvärinen Pekka , Debes Paul V. , Erkinaro Jaakko , Sinclair-Waters Marion , Pritchard Victoria L. , Härkönen Laura S. , Primmer Craig R.
Published: July 2022

One of the most well-known life-history continuums is the fast–slow axis, where ‘fast’ individuals mature earlier than ‘slow’ individuals. ‘Fast’ individuals are predicted to be more active than ‘slow’ individuals because high activity is required to maintain a fast life-history strategy. Recent meta-analyses revealed mixed evidence for such integration. Here, we test whether known life-history genotypes differ in activity expression by using Atlantic salmon (
Salmo salar
) as a model. In salmon, variation in Vgll3, a transcription cofactor, explains approximately 40% of variation in maturation timing. We predicted that the allele related to early maturation (
vgll3
*E) would be associated with higher activity. We used an automated surveillance system to follow approximately 1900 juveniles including both migrants and non-migrants (i.e. smolt and parr fish, respectively) in semi-natural conditions over 31 days (approx. 580 000 activity measurements). In migrants, but not in non-migrants,
vgll3
explained variation in activity according to our prediction in a sex-dependent manner. Specifically, in females the
vgll3
*E allele was related to increasing activity, whereas in males the
vgll3
*L allele (later maturation allele) was related to increasing activity. These sex-dependent effects might be a mechanism maintaining within-population genetic life-history variation.
Crystal structures of WrbA, a spurious target of the salicylidene acylhydrazide inhibitors of type III secretion in Gram-negative pathogens, and verification of improved specificity of next-generation compounds
Authors: Zambelloni Riccardo , Beckham Katherine S.H. , Wu Hong-Jin , Elofsson Mikael , Marquez Rudi , Gabrielsen Mads , Roe Andrew J.
Published: July 2022

The enterohemorrhagic

Escherichia coli

pathotype is responsible for severe and dangerous infections in humans. Establishment of the infection requires colonization of the gastro-intestinal tract, which is dependent on the Type III Secretion System. The Type III Secretion System (T3SS) allows attachment of the pathogen to the mammalian host cell and cytoskeletal rearrangements within the host cell. Blocking the functionality of the T3SS is likely to reduce colonization and therefore limit the disease. This route offers an alternative to antibiotics, and problems with the development of antibiotics resistance. Salicylidene acylhydrazides have been shown to have an inhibitory effect on the T3SS in several pathogens. However, the main target of these compounds is still unclear. Past work has identified a number of putative protein targets of these compounds, one of which being WrbA. Whilst WrbA is considered an off-target interaction, this study presents the effect of the salicylidne acylhydrazide compounds on the activity of WrbA, along with crystal structures of WrbA from

Yersinia pseudotuberculosis

and

Salmonella

serovar Typhimurium; the latter also containing parts of the compound in the structure. We also present data showing that the original compounds were unstable in acidic conditions, and that later compounds showed improved stability.
Effect of an Artificial Intelligence Chest X-Ray Disease Prediction System on the Radiological Education of Medical Students: A Pilot Study
Authors: Dao Lan , Harmouch Sabrina Sofia , Chin Anne , Dao Tien , Thian Zhe , Chartrand-Lefebvre Carl , Cohen Joseph Paul
Published: July 2022

BACKGROUND

We aimed to evaluate the feasibility of implementing Chester, a novel web-based chest X-ray (CXR) interpretation artificial intelligence (AI) tool, in the medical education curriculum and explore its effect on the diagnostic performance of undergraduate medical students.

METHODS

Third-year trainees were randomized in experimental (N=16) and control (N=16) groups and stratified for age, gender, confidence in CXR interpretation, and prior experience. Participants filled a pre-intervention survey, a test exam (Exam1), a final exam (Exam2), and a post-intervention survey. The experimental group was allowed to use Chester during Exam1 while the control group could not. All participants were forbidden from using any resources during Exam2. The diagnostic interpretation of a fellowship-trained chest radiologist was used as the standard of reference. Chester’s performance on Exam1 was 60%. A five-point Likert scale was used to assess students’ perceived confidence before/after the exams as well as Chester’s perceived usefulness.

RESULTS

Using a mixed model for repeated measures (MMRM), it was found that Chester did not have a statistically significant impact on the experimental group’s diagnostic performance nor confidence level when compared to the control group. The experimental group rated Chester’s usefulness at 3.7/5, its convenience at 4.25/5, and their likelihood to reuse it at 4.1/5.

CONCLUSION

Our experience highlights the interest of medical students in using AI tools as educational resources. While the results of the pilot project are inconclusive for now, they demonstrate proof of concept for a repeat experiment with a larger sample and establish a robust methodology to evaluate AI tools in radiological education. Finally, we believe that additional research should be focused on the applications of AI in medical education so students understand this new technology for themselves and given the growing trend of remote learning.
Integrated single-cell sequencing analysis reveals peripheral immune landscape across the human lifespan
Authors: Tong Renyang , Li Ronghong , Zhao Yichao , Luo Lingjie , Zhong Jianmei , Li Zheng , Wei Lin , Chen Yifan , Shi Jianfeng , Gao Yu , Sun Mingze , Lyu Yuyan , Yuan Ancai , Sun Lingyue , Guo Yuping , Wang Honglin , Chen Haoyan , Chen Lei , Li Bin , Lin Wei , Wang Feng , Wang Li , Pu Jun
Published: July 2022

Systematic understanding of immune dynamics across the entire human lifespan at single-cell resolution is currently lacking. Here, we performed single-cell RNA sequencing (scRNA-seq) and single-cell T cell receptor (TCR)/B cell receptor (BCR) sequencing (scTCR/BCR-seq) on over 380,000 peripheral blood mononuclear cells collected from 45 healthy participants aged 0 to over 90 years. We revealed that the functions of T cell subsets were most susceptible to senescence among all PBMCs, featured by increased NF-κB signaling and IFN-γ responses pathways, while reduced telomere maintenance and energy metabolism. We subsequently explored the rewiring of cell-cell interactions among different immune cells across the lifespan and revealed the major alteration of immune checkpoints in T cells within the cellular interaction networks. By combined analysis of scRNA-seq and scTCR-seq, we revealed that 1) GNLY+CD8 Effector T cells exhibited a high clonal expansion with distinct functional signatures in children and the elderly; 2) Naïve CD4+T and naïve CD8+T cells displayed different aging patterns in both transcriptomes and immune repertoires; and 3) CD8+MAIT cells showed a higher cell abundance and clonal diversity in adolescents. Furthermore, we identified a unique cytotoxic B cell subset enriched in children by scRNA-seq and scBCR-seq analysis and experimental validations. In summary, our work provided valuable insights and rich resources for understanding the development and aging of the human immune system across the lifespan.
Networks of Phenological Synchrony Reveal a Highly Interconnected Ecosystem and Potential Vulnerability to Climate-Driven Mismatches
Authors: Garretson Alexis , Feldsine Natalie , Napoli Megan , Long Elizabeth C , Forkner Rebecca E
Published: July 2022

As anthropogenic climate change alters species’ phenology, phenological shifts may cascade to disrupt species interactions to impact ecosystem functioning. We present a 108-year phenology dataset of 8,840 event dates for 251 phenophases for seven amphibian species, 58 birds, 14 insects, and 163 plant species, including 52 species introduced to New York. The dataset was collected at a single location in the Northeastern United States, providing continuity in monitoring since the early 1900s. We show that linear phenology analyses can underestimate the magnitude of phenological shift relative to circular methods, particularly for species experiencing extreme advancements. However, species phenologies are generally advancing, with faster advancements of insects and amphibians compared to birds and plants. Additionally, in our dataset, species with event dates later in the year are advancing more rapidly than species earlier in the year, and this relationship is stronger for animals than for plants. We present a novel, network-based approach for visualizing community and ecosystem-scale phenological synchrony. Using this approach, we find a high degree of synchrony between the monitored species, and this approach reveals that plants are more central in the phenological network, as well as species with phenological events earlier in the year. While many synchronous species are shifting at relatively similar rates and display similar temperature sensitivities, we highlight two species interactions potentially vulnerable to changing climate: Eastern Tent Caterpillars and Monarchs. Our results illustrate the utility of long-term ecological monitoring for investigating ecosystem responses to climate change and identifying potentially vulnerable phenological networks.

Significance Statement

The purpose of this study is to understand how climate change has affected the phenology of an ecological community for over 100+ years. We present a novel approach to analyzing and visualizing community-level phenological data. We find that plants are central to phenological networks, as are species that flower, fruit, or undergo other phenological events earlier in the year. This is important because understanding which species are most central to an ecosystem, as well as which species are vulnerable to climate-driven mismatches (e.g., a butterfly emerges before the flowers that it feeds on bloom) that could cascade through an ecosystem.
Brassinosteroids signaling component SlBZR1 promotes fruit ripening in tomato
Authors: Meng Fanliang , Liu Haoran , Hu Songshen , Jia Chengguo , Zhang Min , Li Songwen , Li Yuanyuan , Lin Jiayao , Jian Yue , Wang Mengyu , Shao Zhiyong , Mao Yuanyu , Liu Lihong , Wang Qiaomei
Published: July 2022

Fruit ripening evolved to be attractive to frugivores that derive energy and nutrition from the fruits in exchange for assisting seed dispersal, which is accompanied by the dramatically change of fruit characteristics, including color, aroma, and texture. The plant hormone ethylene plays a key role in climacteric fruit ripening, while the role of other phytohormones as well as their cross talk with ethylene in modulating fruit ripening remains elusive. Here, we report growth-promoting phytohormone brassinosteroids promote fruit ripening in tomato through regulation of ethylene biosynthesis. Exogenous BR treatment and the increase of endogenous BR content in SlCYP90B3-OE promoted ethylene production and fruit ripening. SlBZR1, a central component and positive regulator of BR signaling pathway, promotes ethylene production and carotenoid accumulation through direct transcriptional regulation of SlACO1, SlACO3 and SlPSY1. Furthermore, SlBIN2, a negative regulator of BR signaling upstream of SlBZR1, decreases ethylene production and carotenoid accumulation. Together, our results demonstrate that BR signaling integrates ethylene and carotenoid biosynthetic pathway to regulate fruit ripening.
Yttrium-iron garnet magnetometer in MEG: Advance towards multi-channel arrays
Authors: Skidchenko E. , Butorina A. , Ostras M. , Vetoshko P. , Kuzmichev A. , Yavich N. , Malovichko M. , Koshev N.
Published: July 2022

Recently, a new kind of sensor applicable in magnetoencephalography (MEG) has been presented: a solid-state yttrium-iron garnet magnetometer (YIGM). The feasibility of YIGM was proved in alpha-rhythm registration experiment. In the current paper, we propose the analysis of lead-field matrices for different possible YIGM multichannel on-scalp sensor layouts with respect to the information theory. We use real noise level of the new sensor to compute signal power, signal-to-noise ration (SNR) and total information capacity, and compare them with corresponding metrics that can be obtained with well-established MEG systems: based on superconducting quantum interference devices (SQUIDs) and optically-pumped magnetometers (OPMs). This simulation study is aimed to shed some light on the direction for further development of YIGM sensor, namely creation of multi-channel YIG-MEG.