bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk of heart disease following treatment for breast cancer – results from a population-based cohort study
Authors: Yang Haomin , Bhoo-Pathy Nirmala , Brand Judith S , Hedayati Elham , Grassmann Felix , Zeng Erwei , Bergh Jonas , Bian Weiwei , Ludvigsson Jonas F , Hall Per , Czene Kamila
Published: March 2022

Background:

There is a rising concern about treatment-associated cardiotoxicities in breast cancer patients. This study aimed to determine the time- and treatment-specific incidence of arrhythmia, heart failure, and ischemic heart disease in women diagnosed with breast cancer.

Methods:

A register-based matched cohort study was conducted including 8015 breast cancer patients diagnosed from 2001 to 2008 in the Stockholm-Gotland region and followed up until 2017. Time-dependent risks of arrhythmia, heart failure, and ischemic heart disease in breast cancer patients were assessed using flexible parametric models as compared to matched controls from general population. Treatment-specific effects were estimated in breast cancer patients using Cox model.

Results:

Time-dependent analyses revealed long-term increased risks of arrhythmia and heart failure following breast cancer diagnosis. Hazard ratios (HRs) within the first year of diagnosis were 2.14 (95% CI = 1.63–2.81) for arrhythmia and 2.71 (95% CI = 1.70–4.33) for heart failure. HR more than 10 years following diagnosis was 1.42 (95% CI = 1.21–1.67) for arrhythmia and 1.28 (95% CI = 1.03–1.59) for heart failure. The risk for ischemic heart disease was significantly increased only during the first year after diagnosis (HR = 1.45, 95% CI = 1.03–2.04). Trastuzumab and anthracyclines were associated with increased risk of heart failure. Aromatase inhibitors, but not tamoxifen, were associated with risk of ischemic heart disease. No increased risk of heart disease was identified following locoregional radiotherapy.

Conclusions:

Administration of systemic adjuvant therapies appears to be associated with increased risks of heart disease. The risk estimates observed in this study may aid adjuvant therapy decision-making and patient counseling in oncology practices.

Funding:

This work was supported by the Swedish Research Council (grant no: 2018-02547); Swedish Cancer Society (grant no: CAN-19-0266); and FORTE (grant no: 2016-00081).
SARS-CoV-2 Nsp14 mediates the effects of viral infection on the host cell transcriptome
Authors: Zaffagni Michela , Harris Jenna M , Patop Ines L , Pamudurti Nagarjuna Reddy , Nguyen Sinead , Kadener Sebastian
Published: March 2022

Viral infection involves complex set of events orchestrated by multiple viral proteins. To identify functions of SARS-CoV-2 proteins, we performed transcriptomic analyses of cells expressing individual viral proteins. Expression of Nsp14, a protein involved in viral RNA replication, provoked a dramatic remodeling of the transcriptome that strongly resembled that observed following SARS-CoV-2 infection. Moreover, Nsp14 expression altered the splicing of more than 1000 genes and resulted in a dramatic increase in the number of circRNAs, which are linked to innate immunity. These effects were independent of the Nsp14 exonuclease activity and required the N7-guanine-methyltransferase domain of the protein. Activation of the NFkB pathway and increased expression of CXCL8 occurred early upon Nsp14 expression. We identified IMPDH2, which catalyzes the rate-limiting step of guanine nucleotides biosynthesis, as a key mediator of these effects. Nsp14 expression caused an increase in GTP cellular levels, and the effect of Nsp14 was strongly decreased in the presence of IMPDH2 inhibitors. Together, our data demonstrate an unknown role for Nsp14 with implications for therapy.
Microtubule rescue at midzone edges promotes overlap stability and prevents spindle collapse during anaphase B
Authors: Lera-Ramirez Manuel , Nédélec François J , Tran Phong T
Published: March 2022

During anaphase B, molecular motors slide interpolar microtubules to elongate the mitotic spindle, contributing to the separation of chromosomes. However, sliding of antiparallel microtubules reduces their overlap, which may lead to spindle breakage, unless microtubules grow to compensate sliding. How sliding and growth are coordinated is still poorly understood. In this study, we have used the fission yeast S. pombe to measure microtubule dynamics during anaphase B. We report that the coordination of microtubule growth and sliding relies on promoting rescues at the midzone edges. This makes microtubules stable from pole to midzone, while their distal parts including the plus ends alternate between assembly and disassembly. Consequently, the midzone keeps a constant length throughout anaphase, enabling sustained sliding without the need for a precise regulation of microtubule growth speed. Additionally, we found that in S. pombe, which undergoes closed mitosis, microtubule growth speed decreases when the nuclear membrane wraps around the spindle midzone.
Minimal requirements for a neuron to coregulate many properties and the implications for ion channel correlations and robustness
Authors: Yang Jane , Shakil Husain , Ratté Stéphanie , Prescott Steven A
Published: March 2022

Neurons regulate their excitability by adjusting their ion channel levels. Degeneracy – achieving equivalent outcomes (excitability) using different solutions (channel combinations) – facilitates this regulation by enabling a disruptive change in one channel to be offset by compensatory changes in other channels. But neurons must coregulate many properties. Pleiotropy – the impact of one channel on more than one property – complicates regulation because a compensatory ion channel change that restores one property to its target value often disrupts other properties. How then does a neuron simultaneously regulate multiple properties? Here, we demonstrate that of the many channel combinations producing the target value for one property (the single-output solution set), few combinations produce the target value for other properties. Combinations producing the target value for two or more properties (the multioutput solution set) correspond to the intersection between single-output solution sets. Properties can be effectively coregulated only if the number of adjustable channels (nin) exceeds the number of regulated properties (nout). Ion channel correlations emerge during homeostatic regulation when the dimensionality of solution space (nin − nout) is low. Even if each property can be regulated to its target value when considered in isolation, regulation as a whole fails if single-output solution sets do not intersect. Our results also highlight that ion channels must be coadjusted with different ratios to regulate different properties, which suggests that each error signal drives modulatory changes independently, despite those changes ultimately affecting the same ion channels.
Targeting the Annexin A1-FPR2/ALX pathway for host-directed therapy in dengue disease
Authors: Costa Vivian Vasconcelos , Sugimoto Michelle A , Hubner Josy , Bonilha Caio S , Queiroz-Junior Celso Martins , Gonçalves-Pereira Marcela Helena , Chen Jianmin , Gobbetti Thomas , Libanio Rodrigues Gisele Olinto , Bambirra Jordana L , Passos Ingredy B , Machado Lopes Carla Elizabeth , Moreira Thaiane P , Bonjour Kennedy , Melo Rossana CN , Oliveira Milton AP , Andrade Marcus Vinicius M , Sousa Lirlândia Pires , Souza Danielle Gloria , Santiago Helton da Costa , Perretti Mauro , Teixeira Mauro Martins
Published: March 2022

Host immune responses contribute to dengue’s pathogenesis and severity, yet the possibility that failure in endogenous inflammation resolution pathways could characterise the disease has not been contemplated. The pro-resolving protein Annexin A1 (AnxA1) is known to counterbalance overexuberant inflammation and mast cell (MC) activation. We hypothesised that inadequate AnxA1 engagement underlies the cytokine storm and vascular pathologies associated with dengue disease. Levels of AnxA1 were examined in the plasma of dengue patients and infected mice. Immunocompetent, interferon (alpha and beta) receptor one knockout (KO), AnxA1 KO, and formyl peptide receptor 2 (FPR2) KO mice were infected withdengue virus(DENV) and treated with the AnxA1 mimetic peptide Ac2-26for analysis. In addition, the effect of Ac2-26on DENV-induced MC degranulation was assessed in vitro and in vivo. We observed that circulating levels of AnxA1 were reduced in dengue patients and DENV-infected mice. Whilst the absence of AnxA1 or its receptor FPR2 aggravated illness in infected mice, treatment with AnxA1 agonistic peptide attenuated disease manifestationsatteanuated the symptoms of the disease. Both clinical outcomes were attributed to modulation of DENV-mediated viral load-independent MC degranulation. We have thereby identified that altered levels of the pro-resolving mediator AnxA1 are of pathological relevance in DENV infection, suggesting FPR2/ALX agonists as a therapeutic target for dengue disease.
Measuring the tolerance of the genetic code to altered codon size
Authors: DeBenedictis Erika Alden , Söll Dieter , Esvelt Kevin M
Published: March 2022

Translation using four-base codons occurs in both natural and synthetic systems. What constraints contributed to the universal adoption of a triplet codon, rather than quadruplet codon, genetic code? Here, we investigate the tolerance of the Escherichia coli genetic code to tRNA mutations that increase codon size. We found that tRNAs from all 20 canonical isoacceptor classes can be converted to functional quadruplet tRNAs (qtRNAs). Many of these selectively incorporate a single amino acid in response to a specified four-base codon, as confirmed with mass spectrometry. However, efficient quadruplet codon translation often requires multiple tRNA mutations. Moreover, while tRNAs were largely amenable to quadruplet conversion, only nine of the twenty aminoacyl tRNA synthetases tolerate quadruplet anticodons. These may constitute a functional and mutually orthogonal set, but one that sharply limits the chemical alphabet available to a nascent all-quadruplet code. Our results suggest that the triplet codon code was selected because it is simpler and sufficient, not because a quadruplet codon code is unachievable. These data provide a blueprint for synthetic biologists to deliberately engineer an all-quadruplet expanded genetic code.
Video captioning based on vision transformer and reinforcement learning
Authors: Zhao Hong , Chen Zhiwen , Guo Lan , Han Zeyu
Published: March 2022

Global encoding of visual features in video captioning is important for improving the description accuracy. In this paper, we propose a video captioning method that combines Vision Transformer (ViT) and reinforcement learning. Firstly, Resnet-152 and ResNeXt-101 are used to extract features from videos. Secondly, the encoding block of the ViT network is applied to encode video features. Thirdly, the encoded features are fed into a Long Short-Term Memory (LSTM) network to generate a video content description. Finally, the accuracy of video content description is further improved by fine-tuning reinforcement learning. We conducted experiments on the benchmark dataset MSR-VTT used for video captioning. The results show that compared with the current mainstream methods, the model in this paper has improved by 2.9%, 1.4%, 0.9% and 4.8% under the four evaluation indicators of LEU-4, METEOR, ROUGE-L and CIDEr-D, respectively.
Inhibition of Connexin 43 reverses ox-LDL-mediated inhibition of autophagy in VSMC by inhibiting the PI3K/Akt/mTOR signaling pathway
Authors: Qin Xuqing , He Wenjun , Yang Rui , Liu Luqian , Zhang Yingying , Li Li , Si Junqiang , Li Xinzhi , Ma Ketao
Published: March 2022

Background

Oxidized low-density lipoproteins (ox-LDL) may induce foam cell formation from the vascular smooth muscle cell (VSMC) by inhibiting VSMC autophagy. This process accelerates the formation of atherosclerosis (AS). Connexin 43 (Cx43), which is the most widely distributed connexin in VSMC is associated with autophagy. However, the mechanism of action and the involvement of Cx43 in ox-LDL-inhibited VSMC autophagy remain unclear.

Methods

The primary VSMC were obtained and identified, before primary VSMC were pretreated with an inhibitor (Cx43-specific inhibitor Gap26 and PI3K inhibitor LY294002) and stimulated with ox-LDL.

Results

Ox-LDL not only inhibited autophagy in VSMC via downregulation of autophagy-related proteins (such as Beclin 1, LC3B, p62), but also increased Cx43 protein levels. Then we added Gap26 to VSMC in the ox-LDL+Gap26 group, in which autophagy-related proteins were increased and the accumulation of lipid droplets was reduced. These result suggested that an enhanced level of autophagy and an alleviation of lipid accumulation might be caused by inhibiting Cx43 in VSMC. The phosphorylation levels of PI3K, AKT, mTOR were increased by ox-LDL, thus down-regulating autophagy-related proteins. However, this situation was partially reversed by the Gap26. Moreover, Cx43 expression were decreased by LY294002 in ox-LDL-induced VSMCs.

Conclusion

Inhibiting Cx43 may activate VSMC autophagy to inhibit foam cell formation by inhibiting the PI3K/AKT/mTOR signaling pathway.
Оксилипины бактерий: ключ к многоклеточности и борьбе с устойчивостью к антибиоткам?, "Природа"
Authors: Куракин Георгий Федорович
Published: March 2022

Оксилипины широкого распространены среди многоклеточных эукариот как медиаторы межклеточной сигнализации. Но их функции у бактерий остаются плохо изученными. Наше недавнее исследование позволило выдвинуть интригующие гипотезы и стало причиной интересных дискуссий о бактериальной оксилипиновой сигнализации. Возможно, знание ее механизмов не только откроет новые страницы в изучении эволюции многоклеточности, но и позволит более успешно бороться с антибиотикорезистентностью.
Общество Леденцова и развитие химии в России, "Природа"
Authors: Смирнова Мария Николаевна , Иванов Владимир Константинович
Published: March 2022

В 2022 г. исполняется 180 лет со дня рождения вологодского купца первой гильдии, мецената Х.С.Леденцова. Созданное в 1909 г. согласно его завещанию Общество содействия успехам опытных наук и их практических применений на протяжении восьми лет оказывало всестороннюю помощь многим ученым, что определило развитие различных областей науки в нашей стране, в том числе и химии. Исследования таких выдающихся российских химиков, как А.Е.Чичибабин, Н.Д.Зелинский, И.А.Каблуков, Л.А.Чугаев, были реализованы во многом благодаря поддержке Общества Леденцова. Ученых обеспечили всем необходимым: лабораториями, оборудованием, приборами, реактивами. Традиции и уникальный опыт Общества Леденцова не утратили актуальности и в XXI в., их изучение имеет важное значение для развития науки в России.
СТАТУС ЦЕРКВИ И ЦЕРКОВНОГО ПРАВА НА ЧЕШСКИХ ЗЕМЛЯХ В СРЕДНИЕ ВЕКА, "Средние века"
Authors: Крафл П.
Published: March 2022

Развитие церковного права в средневековой Чехии можно разделить на несколько этапов. Для раннего этапа, периода существования Чешского княжества, типичным было применение к церкви принципа права собственности. Тот, кто основал храм, был его владельцем. Это ограничивало возможности епископа влиять на действия священника такого частного храма и следить за исполнением церковных канонов. Важным памятником, документирующим постепенное устранение нехристианских пережитков, являются Гнезненские указы чешского князя Бржетислава. В XII в. в скриптории в Оломоуце были изготовлены копии правовых сборников Бурхарда Вормсского и Иво Шартрского. Дальнейшим изменениям способствовала деятельность Пражского епископа Ондржея (1214–1224) по осуществлению в его диоцезе решений IV Латеранского собора и программы папства. XIII – первая половина XIV в. прошли под знаком внедрения новых принципов в жизнь общества: соблюдалась судебная неприкосновенность духовенства и церковного имущества, патронатное право заменило право частной церкви. Период со второй половины XIV до начала XV в. стал временем наибольшего влияния и значения церковного права. Частью программы гуситов был полный отказ от церковного права. После гуситской «революции» не произошло восстановления сложившегося ранее порядка, церковное право в общественном сознании было подчинено праву светскому.
ПЕЧАТНЫЕ АКТЫ КАРЛА V ПЕРИОДА ШМАЛЬКАЛЬДЕНСКОЙ ВОЙНЫ ИЗ АРХИВА САНКТ-ПЕТЕРБУРГСКОГО ИНСТИТУТА ИСТОРИИ РАН: К ИСТОРИИ СРЕДСТВ МАССОВОЙ ИНФОРМАЦИИ И ПРОПАГАНДЫ НАЧАЛА НОВОГО ВРЕМЕНИ, "Средние века"
Authors: Таценко Т.Н.
Published: March 2022

Статья посвящена двум подлинным печатным актам императора Священной Римской империи Карла V из собрания Н.П. Лихачева Научно-исторического архива СПбИИ РАН, относящимся к истории Шмалькальденской войны в Германии между католиками и протестантами (1546–1547). Имеются в виду «Послание к некоторым имперским городам» от 17 июня 1546 г. (5/603) и «Мандат Мельхиору, епископу Вюрцбургскому, и подданным всех сословий Франконии» от 28 ноября 1546 г. (3/603). Имевшие пропагандистский характер и цели и размноженные с помощью печатного станка документы рассматриваются как средства массовой информации и пропаганды. В исследовании в историческом контексте анализируются цели автора печатных посланий, круг их адресатов, планируемое воздействие и стратегии убеждения, взятые на вооружение составителями текстов. Важное значение придается анализу стиля, образности языка и метафорам как средствам выразительности печатного слова. В статье также разбираются формуляр и композиция актов, даны и внешние характеристики. В приложении публикуется текст «Мандата Мельхиору, епископу Вюрцбургскому, и подданным всех сословий Франконии» от 28 ноября 1546 г. (3/603) и его перевод на русский язык.
ЕВРЕЙСКО-ХРИСТИАНСКИЕ ОТНОШЕНИЯ НА ПЕПЕЛИЩЕ: СПОР ВОКРУГ ЦЕРКОВНОГО УЧАСТКА В БРЕСТЕ В 1669–1671 гг., "Средние века"
Authors: Шпирт А.М.
Published: March 2022

В статье предложен анализ судебного конфликта между еврейской общиной Бреста и униатским капитулом в 1669–1671 гг. Предполагая построить на месте еврейских домов церковь, брестский капитул потребовал от евреев освободить занимаемое ими церковное владение. Автор дает сравнительный анализ отношений между евреями и униатским и католическим духовенством, а также показывает ритуальные и символические аспекты конфликта, который развивался на фоне сложных отношений между униатским митрополитом и владимирским (брестским) епископом. Несмотря на то что большинство использованных в статье источников опубликовано, обращение к новым подходам из социальной истории и культурной антропологии помогает осветить проблемы религиозного насилия и конфессиональных отношений в новом свете.
Native to Nemesis: a cultural and environmental history of the Noisy Miner 1788 - 2019
Authors: Beggs Richard
Published: March 2022

1878: “…gallant little birds” (Wagga Wagga Advertiser)

1915: “… the carol of the magpie is eclipsed by the song of the miner” (Emu)

2004: “…the mafia of the bird world” (Australian Broadcasting Corporation)

2015: “I hate those f***in things” (RedditAustralia)

Through the 19th Century and the first half of the 20th Century, notwithstanding its role as an agricultural pest, the Noisy Miner Manorina melanocephala was considered with affection by colonial society. The species’ reputation has been severely damaged in recent decades, however, on account of its violent tendencies towards smaller woodland birds, including many of conservation concern. Aggressive exclusion of small woodland birds from potential woodland habitat by Noisy Miners was declared a Key Threatening Process under federal conservation legislation in 2014. Given that Noisy Miners, other woodland birds, and the post-ice age woodland environment have been co-evolving for at least 10 000 years, how did the natural competitive behaviour of Noisy Miners become an ecological problem? In this paper I review historical references to Noisy Miners and current research on the ecology of the species to construct a trajectory of change. Culturally, these changes include a shift in attitudes to the species from agricultural pest and popular native bird to a vilified, “overabundant” native species and nemesis of small woodland birds. Ecologically, changes have included an expansion in distribution and abundance of Noisy Miners. This has led to an increase in scale of the effects of Noisy Miner aggression on small woodland birds. The historical record contains many references to Noisy Miner aggression against other species, the first appearing within four years of the arrival of the First Fleet in 1788. Evidence that such aggression could affect the abundance and distribution of small woodland birds, however, appears only in the period after World War II. The changing ecological role of Noisy Miners, and the associated changes in cultural attitude to the species, appear linked to the loss, fragmentation and degradation of native woodland in eastern Australia since the introduction of European agriculture and urbanization. In particular, the change in ecological role of the Noisy Miner appears to be linked to the accelerated rates of deforestation in the post-war period. Such broadscale habitat modification has both benefitted Noisy Miners and exacerbated declines in woodland-dependent small birds.
Through the Cowgate
Authors: Jones Elizabeth , Crone Anne , Cross Morag , Franklin Julie , Haston Sarah-Jane , Holmes N M McQ , Lancaster Stephen , Mighall T M , Reilly Eileen , Thomas Clare , Timpany Scott , Tourunen Auli
Published: March 2022

Excavations in the grounds of St Patrick's Church, Edinburgh (NGR: NT 26123 73610) were undertaken by Headland Archaeology from November 2006 to February 2007 on behalf of the Archdiocese of St Andrews and Edinburgh in advance of the construction of a hotel on the site. Soil analyses suggested that flash floods had swept through this part of Cowgate up until the early development of the medieval town upslope in the 11th–12th centuries. This early pattern was followed by the gradual build-up of material washed downslope from the High Street; this contained midden material and dung beetles, illustrating the nearby presence of the town. The site lay outwith the bounds of the burgh until the 14th century, when a substantial ditch was cut across the site, believed to be the medieval town boundary. The ditch was backfilled in the 15th century and finds and samples have revealed a vivid picture of life in the medieval town. The ditch was a stinking rubbish dump for many kinds of human and animal detritus, which illustrates that the Cowgate was a busy thoroughfare to the town's markets and contained a variety of industries, including horn working. After the ditch was filled in deep midden deposits, characteristic of this area of Edinburgh, built up on the site.
The therapeutic capacity of bone marrow MSC‐derived extracellular vesicles in Achilles tendon healing is passage‐dependent and indicated by specific glycans
Authors: Hayashi Yuta , Yimiti Dilimulati , Sanada Yohei , Ding Chenyang , Omoto Takenori , Ogura Toshihiko , Nakasa Tomoyuki , Ishikawa Masakazu , Hiemori Keiko , Tateno Hiroaki , Miyaki Shigeru , Adachi Nobuo
Published: March 2022

The therapeutic potential of mesenchymal stem cell (MSC)‐derived extracellular vesicles (EVs) for various diseases and tissue repair is attracting attention. Here, EVs from conditioned medium of human bone marrow MSCs at passage 5 (P5) and passage 12 (P12) were analysed using mouse Achilles tendon rupture model and lectin microarray. P5 MSC‐EVs accelerated Achilles tendon healing compared with P12 MSC‐EVs. Fucose‐specific lectin TJA‐II was indicated as a glycan marker for therapeutic MSC‐EVs. The present study demonstrated that early passaged MSC‐EVs promote Achilles tendon healing compared with senescent MSC‐EVs. Glycans on MSC‐EVs might provide useful tools to establish a quality control and isolation system for therapeutic MSC‐EVs in regenerative medicine.
Nanoscale‐tipped wire array injections transfer DNA directly into brain cells ex vivo and in vivo
Authors: Numano Rika , Goryu Akihiro , Kubota Yoshihiro , Sawahata Hirohito , Yamagiwa Shota , Matsuo Minako , Iimura Tadahiro , Tei Hajime , Ishida Makoto , Kawano Takeshi
Published: March 2022

Genetic modification to restore cell functions in the brain can be performed through the delivery of biomolecules in a minimally invasive manner into live neuronal cells within brain tissues. However, conventional nanoscale needles are too short (lengths of ~10 µm) to target neuronal cells in ~1‐mm‐thick brain tissues because the neuronal cells are located deep within the tissue. Here, we report the use of nanoscale‐tipped wire (NTW) arrays with diameters < 100 nm and wire lengths of ~200 µm to address biomolecule delivery issues. The NTW arrays were manufactured by growth of silicon microwire arrays and nanotip formation. This technique uses pinpoint, multiple‐cell DNA injections in deep areas of brain tissues, enabling target cells to be marked by fluorescent protein (FP) expression vectors. This technique has potential for use for electrophysiological recordings and biological transfection into neuronal cells. Herein, simply pressing an NTW array delivers and expresses plasmid DNA in multiple‐cultured cells and multiple‐neuronal cells within a brain slice with reduced cell damage. Additionally, DNA transfection is demonstrated using brain cells ex vivo and in vivo. Moreover, knockdown of a critical clock gene after injecting a short hairpin RNA (shRNA) and a genome‐editing vector demonstrates the potential to genetically alter the function of living brain cells, for example, pacemaker cells of the mammalian circadian rhythms. Overall, our NTW array injection technique enables genetic and functional modification of living cells in deep brain tissue areas, both ex vivo and in vivo.
‘Everyone is trying to outcompete each other’: a qualitative study of medical student attitudes to a novel peer‐assessed undergraduate teamwork module
Authors: Watson Helen R. , Dolley Mary‐Kate , Perwaiz Mohammad , Saxelby Jocelyn , Bertone Gianluca , Burr Steven , Collett Tracey , Jeffery Robert , Zahra Daniel
Published: March 2022

The centrality of teamwork in ensuring the effective functioning of institutions across all sectors is undeniable. However, embedding teamwork into higher education has been hampered due to a range of deeply entrenched practices associated broadly with the foregrounding of knowledge, beliefs about the place of skill training and routines of assessment. As a result, despite an urgent need to address teamwork, little progress has been made with respect to progressing teamwork education. We have designed and evaluated a novel teamwork module delivered to fourth‐year undergraduate medical students involving placements, a cocreated piece of work, reflection and summative peer assessment. This paper aimed to investigate whether the module increased students’ insight into teamwork, including their own skill development, and whether their perceptions of teamwork changed. Throughout the evaluation, students played a key role, with four final‐year medical students working alongside others in the multidisciplinary project team. Five distinct themes emerged from our in‐depth, semi‐structured interviews: (a) importance and meaning; (b) insight into skill development; (c) transferability; (d) peer assessment; and (e) resistance to teamwork education. Themes had positive and negative components, and student perceptions changed in multiple ways after experiencing a longitudinal educational opportunity to develop their teamwork skills. Before practice, students focused on superficial explanations and on where they might improve. In contrast, after practice, students conveyed deeper insights, contextualisation, focus on how they might improve, and shared structured reflection.
Evaluation of ultralow‐dose computed tomography on detection of pulmonary nodules in overweight or obese adult patients
Authors: Guo Xiaowan , Jia Dezhao , He Lei , Jia Xudong , Zhang Danqing , Dou Yana , Shen Shanshan , Ji Hong , Zhang Shuqian , Chen Yingmin
Published: March 2022

Purpose

To evaluate the accuracy of pulmonary nodule (PN) detection in overweight or obese adult patients using ultralow‐dose computed tomography (ULDCT) with tin filtration at 100 kV and advanced model‐based iterative reconstruction (ADMIRE).

Methods

Eighty‐one patients with body mass indices of ≥25 kg/m2 were enrolled. All patients underwent low‐dose chest CT (LDCT), followed by ULDCT. Two radiologists experienced in LDCT established the standard of reference (SOR) for PNs. The number, type, size, and location of PNs were identified in the SOR. Effective dose, objective image quality (IQ), and subjective IQ based on two radiologists’ scores were compared between ULDCT and LDCT. The detection performances of radiologists based on ULDCT were calculated according to the nodule analyses. Logistic regression was used to test for independent predictors of PN detection sensitivity.

Results

Both the effective dose and objective IQ were lower for ULDCT than for LDCT (both p < 0.001). Both radiologists rated the subjective IQ of the overall IQ on ULDCT to be diagnostically sufficient. In total, 234 nodules (mean diameter, 3.4 ± 1.9 mm) were classified into 32 subsolid, 149 solid, and 53 calcified nodules according to the SOR. The overall sensitivity of ULDCT for nodule detection was 93.6%. Based on multivariate analyses, the nodule types (p = 0.015) and sizes (p = 0.013) were independent predictors of nodule detection.

Conclusions

Compared with LDCT, ULDCT with tin filtration at 100 kV and ADMIRE could significantly reduce the radiation dose in overweight or obese patients while maintaining good sensitivity for nodule detection.
Quantitative evaluation of upper limb ataxia in spinocerebellar ataxias
Authors: Kishimoto Yoshiyuki , Hashizume Atsushi , Imai Yuta , Nakatochi Masahiro , Yamada Shinichiro , Ito Daisuke , Torii Ryota , Nagano Yoshitaka , Fujimoto Hideo , Katsuno Masahisa
Published: March 2022

Objective

To quantitatively evaluate upper limb ataxia using a novel pen‐like sensor device in patients with spinocerebellar ataxia (SCA) and to assess its validity, reliability, and sensitivity to disease progression.

Methods

We designed a cross‐sectional and longitudinal study of patients with SCA and healthy controls. Upper limb ataxia was evaluated using a device that measures the three‐dimensional position every 10 msec. Participants were instructed to move a pen‐like part of the device iteratively between two buttons. We evaluated the time, length, velocity, and variation coefficient of the stroke, and calculated the distortion index using the mean squared error. The following scales were also evaluated: Scale for the Assessment and Rating of Ataxia (SARA), the International Cooperative Ataxia Rating Scale (ICARS), and the nine‐hole pegboard test. Subjects were followed 12 months after the baseline evaluation.

Results

A total of 42 patients with SCA and 33 healthy controls were enrolled and evaluated. For all ataxia indices measured using the device there were significant differences between healthy controls and patients with SCA. Among the ataxia indices, the distortion index showed the strongest correlation with the SARA and ICARS upper limb score (Pearson's r = 0.647 and 0.722, respectively). Test–retest reliability was high for most of the ataxia indices. In the longitudinal analysis, the distortion index showed high standardized response mean and adjusted effect size, regardless of disease severity.

Interpretation

Our study demonstrated that the distortion index is a reliable functional marker that is sensitive to longitudinal change in patients with SCA.
New approaches for the quantification and targeting of noradrenergic dysfunction in Alzheimer's disease
Authors: David Michael , Malhotra Paresh A.
Published: March 2022

There is clear, early noradrenergic dysfunction in Alzheimer's disease. This is likely secondary to pathological tau deposition in the locus coeruleus, the pontine nucleus that produces and releases noradrenaline, prior to involvement of cortical brain regions. Disruption of noradrenergic pathways affects cognition, especially attention, impacting memory and broader functioning. Additionally, it leads to autonomic and neuropsychiatric symptoms. Despite the strong evidence of noradrenergic involvement in Alzheimer's, there are no clear trial data supporting the clinical use of any noradrenergic treatments. Several approaches have been tried, including proof‐of‐principle studies and (mostly small scale) randomised controlled trials. Treatments have included pharmacotherapies as well as stimulation. The lack of clear positive findings is likely secondary to limitations in gauging locus coeruleus integrity and dysfunction at an individual level. However, the recent development of several novel biomarkers holds potential and should allow quantification of dysfunction. This may then inform inclusion criteria and stratification for future trials. Imaging approaches have improved greatly following the development of neuromelanin‐sensitive sequences, enabling the use of structural MRI to estimate locus coeruleus integrity. Additionally, functional MRI scanning has the potential to quantify network dysfunction. As well as neuroimaging, EEG, fluid biomarkers and pupillometry techniques may prove useful in assessing noradrenergic tone. Here, we review the development of these biomarkers and how they might augment clinical studies, particularly randomised trials, through identification of patients most likely to benefit from treatment. We outline the biomarkers with most potential, and how they may transform symptomatic therapy for people living with Alzheimer's disease.
Obstacle avoidance and model‐free tracking control for home automation using bio‐inspired approach
Authors: Khan Ameer Tamoor , Li Shuai , Li Zhan
Published: March 2022

This article proposes a control algorithm for obstacle avoidance and trajectory tracking for a redundant‐manipulator in smart‐homes. The redundancy provides dexterity and flexibility for the applications like picking, dropping, and transporting objects, tracking predefined paths while avoiding obstacles. The obstacle avoidance is one of the critical problems that need to be addressed. Our proposed algorithm, zeroing neural network with beetle antennae search (ZNNBAS), unifies these two problems into a single constrained optimization problem, which includes a penalty function to reward the optimizer on avoiding obstacles while tracking the reference trajectory. The penalty function is based on the principle of maximizing the minimum distance between the joints of the manipulator and the obstacles. Gilbert Johnson Keerthi (GJK) algorithm is used to calculate the distance between the manipulator and the obstacle as it uses the 3D geometry of the object and manipulator. To test the working of ZNNBAS, we simulated the model of the KUKA LBR robotic manipulator. We used two reference trajectories, that is, hypotrochoid and a character “M,” with an arbitrarily shaped obstacle. The simulation results show that ZNNBAS was able to trace the reference path while successfully avoiding the obstacle accurately.
Silver Clusters of Five Atoms as Highly Selective Antitumoral Agents Through Irreversible Oxidation of Thiols
Authors: Porto Vanesa , Buceta David , Domínguez Blanca , Carneiro Carmen , Borrajo Erea , Fraile María , Davila‐Ferreira Nerea , Arias Iria R. , Blanco José M. , Blanco Maria C. , Devida Juan M. , Giovanetti Lisandro J. , Requejo Félix G. , Hernández‐Garrido Juan C. , Calvino José J. , López‐Haro Miguel , Barone Giampaolo , James Andrew M. , García‐Caballero Tomás , González‐Castaño Diego M. , Treder Martin , Huber Wolfgang , Vidal Anxo , Murphy Michael P. , López‐Quintela M. Arturo , Domínguez Fernando
Published: March 2022

Low atomicity clusters present properties dependent on the size, due to the quantum confinement, with well‐defined electronic structures and high stability. Here it is shown that Ag5 clusters catalyze the complete oxidation of sulfur to S+6. Ag5 catalytic activity increases with different oxidant species in the order O2 ≪ H2O2 < OH•. Selective oxidation of thiols on the cysteine residues of glutathione and thioredoxin is the primary mechanism human cells have to maintain redox homeostasis. Contingent upon oxidant concentration, Ag5 catalyzes the irreversible oxidation of glutathione and thioredoxin, triggering apoptosis. Modification of the intracellular environment to a more oxidized state to mimic conditions within cancer cells through the expression of an activated oncogene (HRASG12V) or through ARID1A mutation, sensitizes cells to Ag5 mediated apoptosis. While cancers evolve to evade treatments designed to target pathways or genetic mutations that drive them, they cannot evade a treatment that takes advantage of aberrant redox homeostasis, which is essential for tumor progression and metastasis. Ag5 has antitumor activity in mice with orthotopic lung tumors reducing primary tumor size, and the burden of affected lymphatic nodes. The findings suggest the unique intracellular redox chemistry of Ag5 may lead to new redox‐based approaches to cancer therapy.
Ferroelastic–Ferroelectric Multiferroicity in van der Waals Rhenium Dichalcogenides
Authors: Jeong Jaehun , Kim Hyeon‐Sik , Kwon Gihyeon , Jeong Kwangsik , Lee Hyangsook , Lee Ji Hye , Park Myunguk , Lee Changjun , Yu Sanghyuck , Kim Heegoo , Im Seongil , Yoo Kyunghwa , Lee Eunha , Cho Mann‐Ho
Published: March 2022

2D multiferroics with combined ferroic orders have gained attention owing to their novel functionality and underlying science. Intrinsic ferroelastic–ferroelectric multiferroicity in single‐crystalline van der Waals rhenium dichalcogenides, whose symmetries are broken by the Peierls distortion and layer‐stacking order, is demonstrated. Ferroelastic switching of the domain orientation and accompanying anisotropic properties is achieved with 1% uniaxial strain using the polymer encapsulation method. Based on the electron localization function and bond dissociation energy of the Re–Re bonds, the change in bond configuration during the evolution of the domain wall and the preferred switching between the two specific orientation states are explained. Furthermore, the ferroelastic switching of ferroelectric polarization is confirmed using the photovoltaic effect. The study provides insights into the reversible bond‐switching process and potential applications based on 2D multiferroicity.
Near‐Infrared Light‐Driven Three‐Dimensional Soft Photonic Crystals Loaded with Upconversion Nanoparticles
Authors: Qiu Yaqi , Yang Yanzhao , Valenzuela Cristian , Zhang Xuan , Yang Mengyuan , Xue Pan , Ma Jiazhe , Liu Ziwei , Wang Ling , Feng Wei
Published: March 2022

Endowing advanced functional three‐dimensional (3D) nanostructures with remote and dynamic controllability is currently in the spotlight of soft‐matter photonics research. Herein, the near‐infrared (NIR) light‐driven reversible and dynamic photonic bandgap modulation of a soft photonic crystal, i.e., blue phase liquid crystals (BPLCs) with 3D nanostructures, is demonstrated through the integration of judiciously designed core‐shell upconversion nanoparticles (UCNPs) and a novel axially‐chiral azobenzene‐based molecular photoswitch. The UCNPs exhibit high UV/vis emissions upon irradiations with 808 nm NIR light, and the intensity ratio of UV/vis luminescence can be facilely modulated through changing the excitation power. With the UCNPs as NIR‐to‐UV/vis light nanotransducers, the chiral molecular photoswitch shows reversible photoisomerization upon modulating the 808 nm NIR light intensity. Furthermore, NIR light‐driven BPLCs loaded with the photoswitch and UCNPs are demonstrated, in which the photonic reflection can red‐shift toward a longer wavelength under 808 nm light irradiation with high‐power density and the blue‐shift took place at lower power density with the same wavelength of light. This work may provide new insights into the large‐scale fabrication of 3D photonic nanostructures with tailorable functionalities toward emerging applications of soft‐matter photonics and future integrated communication technologies.
Electronic Topological Transition as a Route to Improve Thermoelectric Performance in Bi0.5Sb1.5Te3
Authors: Bai Feng‐Xian , Yu Hao , Peng Ya‐Kang , Li Shan , Yin Li , Huang Ge , Chen Liu‐Cheng , Goncharov Alexander F. , Sui Jie‐He , Cao Feng , Mao Jun , Zhang Qian , Chen Xiao‐Jia
Published: March 2022

The electronic structure near the Fermi surface determines the electrical properties of the materials, which can be effectively tuned by external pressure. Bi0.5Sb1.5Te3 is a p‐type thermoelectric material which holds the record high figure of merit at room temperature. Here it is examined whether the figure of merit of this model system can be further enhanced through some external parameter. With the application of pressure, it is surprisingly found that the power factor of this material exhibits λ behavior with a high value of 4.8 mW m−1 K−2 at pressure of 1.8 GPa. Such an enhancement is found to be driven by pressure‐induced electronic topological transition, which is revealed by multiple techniques. Together with a low thermal conductivity of about 0.89 W m−1 K−1 at the same pressure, a figure of merit of 1.6 is achieved at room temperature. The results and findings highlight the electronic topological transition as a new route for improving the thermoelectric properties.
Association between unmanned aerial vehicle high‐throughput canopy phenotyping and soybean yield
Authors: Casagrande Cleiton Renato , Sant'ana Gustavo César , Meda Anderson Rotter , Garcia Alexandre , Souza Carneiro Pedro Crescêncio , Nardino Maicon , Borem Aluizio
Published: March 2022

Identifying agronomic traits correlated to grain yield can be very useful for soybean [Glycine max (L.) Merr.] breeding, especially if these traits can be measured through unmanned aerial vehicle high‐throughput phenotyping rather than through manual measurements. The objective of the present study was to assess the association between canopy coverage and soybean grain yield through different statistical methodologies. A panel with 97 soybean genotypes was evaluated in two field experiments conducted in Paraná State, Brazil. Canopy coverage was determined by using an RGB camera coupled to a drone. Images taken during flights at phenological stages V3‐V4, V5‐V6, V7‐V8, and V9‐R1 were used to calculate canopy coverage based on the green pixel ratio in each experimental unit. There were significant genotype × environment interactions in all evaluated traits. Selective accuracy values (0.73–0.96) revealed indirect yield selection efficiency based on canopy coverage. High genetic correlation estimates (0.76) were observed between grain yield and canopy coverage at flowering in one of the assessed environments. These results were confirmed through genetic correlation coefficient decomposition in direct and indirect effects and of gain estimates presenting indirect selection. Thus, canopy coverage data remotely collected using drones to soybean indirect selection for grain yield can be a promising strategy to accelerate genetic gains in soybean breeding programs.
Adoptive therapy with cytomegalovirus‐specific T cells for cytomegalovirus infection after haploidentical stem cell transplantation and factors affecting efficacy
Authors: Pei Xu‐Ying , Zhao Xiang‐Yu , Liu Xue‐Fei , Mo Xiao‐Dong , Lv Meng , Xu Lan‐Ping , Wang Yu , Chang Ying‐Jun , Zhang Xiao‐Hui , Liu Kai‐Yan , Huang Xiao‐Jun
Published: March 2022

Adoptive therapy with cytomegalovirus (CMV)‐specific cytotoxic T lymphocytes (CMV‐CTLs) has emerged as an effective method for CMV infection. However, the efficacy reportedly ranges from 50% to 90%, and factors affecting anti‐CMV efficacy have not been established. We investigated the safety and efficacy of adoptive therapy with CMV‐CTLs for CMV infection in 190 patients after haploidentical stem cell transplantation (haplo‐SCT), and importantly, we analyzed the main factors affecting antiviral efficacy. The CMV peak titer decreased from 19 (range, 1.0–503.0) × 103 copies/mL to 3.9 (range, 0–112) × 103 copies/mL after CMV‐CTL infusion. The cumulative complete response (CR) rates in the first, fourth, and sixth weeks after the first CMV‐CTL infusion were 37.9% (95% CI 35.0–40.8), 76.8% (95% CI 70.7–82.9), and 89.5% (95% CI 85.2–93.8), respectively. In multivariate analysis, persistent CMV infection prior to CMV‐CTL infusion (hazard ratio [HR] 2.29, 95% CI 1.29–4.06, p = .005) and basiliximab treatment within 2 weeks of CMV‐CTL infusion (HR 1.87, 95% CI 1.06–3.81, p = .031) were independent predictors of poor antiviral efficacy of CMV‐CTL therapy. Our data showed that adoptive therapy with CMV‐CTLs is a safe and effective treatment for CMV infection after haplo‐SCT. Persistent CMV infection and basiliximab treatment are correlated with poor anti‐CMV efficacy of CMV‐CTL therapy.
Measuring the benefits of occupational safety and health research with economic metrics: Insights from the National Institute for Occupational Safety and Health
Authors: Bushnell P. Timothy , Pana‐Cryan Regina , Howard John , Quay Brian , Ray Tapas K.
Published: March 2022

Measuring the ultimate impact of research on health and economic well‐being has presented challenges that have rarely been surmounted, and research on preventing occupational injuries and illnesses is no exception. Nevertheless, there is an increasing need to demonstrate the value of publicly funded research. The National Institute for Occupational Safety and Health (NIOSH) recently contracted with the RAND Corporation to conduct six in‐depth case studies that aimed to quantify the benefits of key NIOSH research efforts using economic metrics. These case studies focused on silica exposure in asphalt pavement milling, firefighter cancer risks, a multi‐industry matching‐grant program for purchase of safety equipment, personal coal dust monitors for coal miners, re‐design of ambulance patient compartments for safety, and workplace amputation surveillance. In this article, we summarize what we learned about how measurement of research benefits may be pursued. We summarize the benefit measurement methods that were used and the results of these research efforts in terms of costs saved, injuries and illnesses prevented, and the statistical value of reductions in risk of death or illness. We then distill some observations about the characteristics of research efforts that make measurement of research benefits feasible and suggest steps that could make it feasible to apply the same methods more widely. We also outline key NIOSH activities that appear not to be amenable to benefit measurement but suggest potentials for progress toward at least partial or qualitative benefit assessment. Finally, we discuss implications of the benefit measurement case studies for strategic research planning.