bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of preoperative frailty assessment in patients with gastrointestinal disease
Authors: Kameyama Hitoshi , Sakata Jun , Hanyu Takaaki , Ichikawa Hiroshi , Nakano Masato , Nagahashi Masayuki , Shimada Yoshifumi , Kobayashi Takashi , Wakai Toshifumi
Published: January 2021

Aim

The role of preoperative frailty assessment in patients with gastrointestinal (GI) disease remains unclear. This study aimed to clarify the relationship between frailty and postoperative outcomes in patients with GI disease.

Methods

This study investigated 42 patients (aged ≥65 years) with GI disease who underwent abdominal surgery. The frailty status was analyzed using the Japanese version of the Cardiovascular Health Study criteria. We also investigated postoperative outcomes.

Results

Of the 42 patients, seven (16.7%) were robust, 24 (57.1%) were prefrail and 11 (26.2%) were frail. Postoperative complications were observed in 45.5% and 63.6% of prefrail and frail patients, respectively, whereas no complications were found in robust patients (P = 0.026). The median hospital stay was 15, 19.5 and 27 days in robust, prefrail and frail patients, respectively (P < 0.01).

Conclusion

Preoperative frailty status based on the Japanese version of the Cardiovascular Health Study criteria is associated with postoperative complication incidence and hospital stay extension in patients with GI disease. Geriatr Gerontol Int 2021; ••: ••–••.
Development and testing of the Satisfaction Questionnaire with Intravenous or Subcutaneous Hemophilia Injection and results from the Phase 3 HAVEN 3 study of emicizumab prophylaxis in persons with haemophilia A without FVIII inhibitors
Authors: Kempton Christine , Trask Peter , Parnes Aric , Niggli Markus , Campinha‐Bacote Avrita , U. Callaghan Michael , O'Connell Niamh , Paz‐Priel Ido , Mahlangu Johnny N.
Published: January 2021

Introduction

Emicizumab is a subcutaneously (SC) administered prophylactic agent for persons with haemophilia A (PwHA). As part of its clinical development, a new instrument was required to measure treatment satisfaction.

Aim

Describe development of the Satisfaction Questionnaire with Intravenous or Subcutaneous Hemophilia Injection (SQ‐ISHI) and its subsequent testing with HAVEN 3 study participants to measure patient satisfaction with emicizumab.

Methods

To develop the SQ‐ISHI, we conducted four rounds of in‐person interviews at five qualitative research facilities. Participants aged ≥12 years with moderate or severe haemophilia A, receiving intravenous factor VIII (FVIII) prophylaxis, provided feedback to optimize content understanding, ease of completion and item relevance. The final SQ‐ISHI was completed by HAVEN 3 participants who previously received FVIII prophylaxis; baseline scores were compared with those at Week 21 or 25 of emicizumab prophylaxis.

Results

Sixty‐three HAVEN 3 participants were eligible to complete the questionnaire and rate their satisfaction on a scale of 0 (‘not at all satisfied’) to 10 (‘extremely satisfied’). Mean ‘overall satisfaction’ with previous FVIII prophylaxis at baseline was 6.9 (95% confidence interval [CI]: 6.2 to 7.7) increasing to 8.8 (95% CI: 8.4 to 9.3) at follow‐up (Week 21/25 of treatment with emicizumab). The greatest improvement was observed in satisfaction with treatment half‐life (mean score at baseline: 5.8 [95% CI: 4.9 to 6.6] vs 8.6 [95% CI: 8.0 to 9.2] at follow‐up).

Conclusion

These results demonstrate that emicizumab prophylaxis leads to greater treatment satisfaction compared with FVIII prophylaxis, reflecting in part the low treatment burden of emicizumab associated with its infrequent, SC administration.
Impact of gestational hypertension and preeclampsia on low birthweight and small‐for‐gestational‐age infants in China: A large prospective cohort study
Authors: Liu Yingying , Li Nan , An Hang , Li Zhiwen , Zhang Le , Li Hongtian , Zhang Yali , Ye Rongwei
Published: January 2021

Studies have shown that maternal blood pressure level is associated with neonatal birthweight, but the results are not exactly consistent. As the most common hypertensive disorders during pregnancy, the mechanism of gestational hypertension and pre‐eclampsia that affect fetal growth remain unclear. Our objective was to examine the association of gestational hypertension and pre‐eclampsia with the risk of low birthweight (LBW) and small‐for‐gestational‐age (SGA). Data were obtained from the China–US Collaborative Project for Neural Tube Defects Prevention, a large population‐based cohort study. We selected participants who were registered in two southern provinces, had exact information on gestational blood pressure and pregnancy outcomes, and were not affected by chronic hypertension. Logistic regression was used to adjust for the effects of the main potential confounders, including age, body mass index, education, occupation, ethnicity, folic acid use, and parity. The overall incidences of LBW and SGA were 2.25% and 5.86%, respectively. The incidences of LBW/SGA were 3.58%/7.58% and 6.02%/10.67% for gestational hypertension and pre‐eclampsia group, relative to 2.11%/5.68% and 2.16%/5.74% for normal group. The adjusted odds ratios associated with gestational hypertension/pre‐eclampsia were 1.77 (95% CI: 1.63, 1.92)/3.01 (95% CI: 2.67, 3.40) for LBW and 1.40 (95% CI: 1.32, 1.48)/2.02 (95% CI: 1.84, 2.22) for SGA, respectively. The early onset of gestational hypertension/pre‐eclampsia appeared to be a relatively more detrimental exposure window for both LBW and SGA. Our results support an association between gestational hypertension or pre‐eclampsia and the increased risk of LBW and SGA.
The Role of Public Opinion in EU Integration: Assessing the Relationship between Elites and the Public during the Refugee Crisis
Authors: Di Mauro Danilo , Memoli Vincenzo
Published: January 2021

While the EU was still recovering from the Great Recession, the refugee crisis polarized and mobilized national and European political spaces, inducing governments to revise their immigration policies. Scholars are presently engaged in academic debate over whether these revisions can be explained by reference to grand theories of European integration. In this context, we ask the following questions. If public opinion favoured ‘constraining’ EU integration, can public concern over the refugee crisis prompt political elites to stand against a regulative solution that would replace the Dublin System? How do these trends align with the grand theories of EU integration? By analysing longitudinal surveys of elites, general public and experts, we show that public rejection of immigrants relates to elites' opposition to a supranational prevalence of EU institutions for setting immigration quotas, thus inhibiting integration on extra‐EU migrants' resettlement.
Insulin actions on hypothalamic glucose‐sensing neurones
Authors: Garcia Stephanie M. , Hirschberg Pamela R. , Sarkar Pallabi , Siegel Dashiel M. , Teegala Suraj B. , Vail Gwyndolin M. , Routh Vanessa H.
Published: January 2021

Subsequent to the discovery of insulin 100 years ago, great strides have been made in understanding its function, especially in the brain. It is now clear that insulin is a critical regulator of the neuronal circuitry controlling energy balance and glucose homeostasis. This review focuses on the effects of insulin and diabetes on the activity and glucose sensitivity of hypothalamic glucose‐sensing neurones. We highlight the role of electrophysiological data in understanding how insulin regulates glucose‐sensing neurones. A brief introduction describing the benefits and limitations of the major electrophysiological techniques used to investigate glucose‐sensing neurones is provided. The mechanisms by which hypothalamic neurones sense glucose are discussed with an emphasis on those glucose‐sensing neurones already shown to be modulated by insulin. Next, the literature pertaining to how insulin alters the activity and glucose sensitivity of these hypothalamic glucose‐sensing neurones is described. In addition, the effects of impaired insulin signalling during diabetes and the ramifications of insulin‐induced hypoglycaemia on hypothalamic glucose‐sensing neurones are covered. To the extent that it is known, we present hypotheses concerning the mechanisms underlying the effects of these insulin‐related pathologies. To conclude, electrophysiological data from the hippocampus are evaluated aiming to provide clues regarding how insulin might influence neuronal plasticity in glucose‐sensing neurones. Although much has been accomplished subsequent to the discovery of insulin, the work described in our review suggests that the regulation of central glucose sensing by this hormone is both important and understudied.
Transient Contingencies: Body as Ecology
Authors: Griffin–Wilson Isla
Published: January 2021

This paper proposes an understanding of the human body as a plural object. Drawing on the ideas of Bennet, Merleau–Ponty, and Wilson, it envisions the body as a complex ecology in which the human biome, the billions of microbial communities that symbiotically live within our bodies, act as a dynamic system of flows and feedbacks within its environments. This body's spatial experiences are not fixed and static, but continuous, fluid, and permeable, in search of novel experiences and homeostasis. By re–imagining what it means to occupy space, we can re–experience our lives as intimately interwoven with the natural world, catalyzing new biophilia, as our body–ecology seeks contentment with “interiors” outside of itself, at home in a dynamic planetary biosphere.
Voice in adolescents' informational writing
Authors: Park Jungyoung , Fang Zhihui
Published: January 2021

Voice is a key component of interpersonal meaning that denotes a writer's value judgement or personal feelings. An important aspect of voice in informational writing is epistemic stance, which indicates a writer's judgement of the information presented. This exploratory study examined adolescents' use of hedges and boosters to convey epistemic stance in their informational writing. Ninety‐three seventh‐grade and ninth‐grade students from one American public school were asked to write a science report oncrocodiliafor a peer audience. The writing corpus was coded for the presence of linguistic markers of hedges and boosters. Statistical analysis reveals that the students as a whole used significantly more boosters than hedges and that there was no significant difference between the two grade levels in the use of hedges or boosters. Moreover, the students drew heavily on everyday language resources to instantiate either hedges or boosters, and there was a lack of lexical diversity in their linguistic choices. These findings suggest that adolescent learners were able to infuse voice in their informational writing but needed to expand their linguistic repertoires for instantiating voice in order to develop advanced literacy.
The association between adverse childhood experiences and childhood obesity: A systematic review
Authors: Schroeder Krista , Schuler Brittany R. , Kobulsky Julia M. , Sarwer David B.
Published: January 2021

Adverse childhood experiences (ACEs) are associated with numerous physical and mental health issues in children and adults. The effect of ACEs on development of childhood obesity is less understood. This systematic review was undertaken to synthesize the quantitative research examining the relationship between ACEs and childhood obesity. PubMed, PsycInfo, and Web of Science were searched in July 2020; Rayyan was used to screen studies, and the Newcastle‐Ottawa Scale was used to assess risk of bias. The search resulted in 6,966 studies screened at title/abstract and 168 at full‐text level. Twenty‐four studies met inclusion criteria. Study quality was moderate, with greatest risk of bias due to method of assessment of ACEs or sample attrition. Findings suggest ACEs are associated with childhood obesity. Girls may be more sensitive to obesity‐related effects of ACEs than boys, sexual abuse appears to have a greater effect on childhood obesity than other ACEs, and co‐occurrence of multiple ACEs may be associated with greater childhood obesity risk. Further, the effect of ACEs on development of childhood obesity may take 2–5 years to manifest. Considered collectively, findings suggest a need for greater attention to ACEs in the prevention and treatment of childhood obesity.
Cytosolic HSC70s repress heat stress tolerance and enhance seed germination under salt stress conditions
Authors: Zhao Huimei , Jan Asad , Ohama Naohiko , Kidokoro Satoshi , Soma Fumiyuki , Koizumi Shinya , Mogami Junro , Todaka Daisuke , Mizoi Junya , Shinozaki Kazuo , Yamaguchi‐Shinozaki Kazuko
Published: January 2021

Heat shock factor A1 (HsfA1) family proteins are the master regulators of the heat stress‐responsive transcriptional cascade in Arabidopsis. Although 70 kDa heat shock proteins (HSP70s) are known to participate in repressing HsfA1 activity, the mechanisms by which they regulate HsfA1 activity have not been clarified. Here, we report the physiological functions of three cytosolic HSP70s, HSC70‐1, HSC70‐2 and HSC70‐3, under normal and stress conditions. Expression of the HSC70 genes was observed in whole seedlings, and the HSC70 proteins were observed in the cytoplasm and nucleus under normal and stress conditions, as were the HsfA1s. hsc70‐1/2 double and hsc70‐1/2/3 triple mutants showed higher thermotolerance than the wild‐type (WT) plants. Transcriptomic analysis revealed the upregulation of heat stress‐responsive HsfA1‐downstream genes in hsc70‐1/2/3 mutants under normal growth conditions, demonstrating that these HSC70s redundantly function as repressors of HsfA1 activity. Furthermore, hsc70‐1/2/3 plants showed a more severe growth delay during the germination stage than the WT plants under high‐salt stress conditions, and many seed‐specific cluster 2 genes that exhibited suppressed expression during germination were expressed in hsc70‐1/2/3 plants, suggesting that these HSC70s also function in the developmental transition from seed to seedling under high‐salt conditions by suppressing the expression of cluster 2 genes.
Bureaucracy, Democracy, and Race: The Limits of Symbolic Representation
Authors: Headley Andrea M. , Wright James E. , Meier Kenneth J.
Published: January 2021

A bureaucracy that is representative of the public it serves—passive representation—can result in both active representation and symbolic representation. Symbolic representation occurs when passive representation improves perceptions of legitimacy and enhances bureaucratic outcomes because the public is more cooperative and more likely to engage in coproduction. We present a new micro‐theory of symbolic representation to show that symbolic benefits of passive representation depend on some level of positive treatment by bureaucrats. We then illustrate the utility of this theory with qualitative interviews from two cities with large populations of people of color and high proportions of police officers of color. The results suggest that increasing the demographic representativeness of the bureaucracy may be a necessary, but not a sufficient, condition for improving the relationship between the public and the bureaucracy.
Non‐specific phospholipases C2 and C6 redundantly function in pollen tube growth via triacylglycerol production in Arabidopsis
Authors: Bose Debayan , Ngo Anh H. , Nguyen Van C. , Nakamura Yuki
Published: January 2021

Non‐specific phospholipase Cs (NPCs) are responsible for membrane lipid remodeling that involves hydrolysis of the polar head group of membrane phospholipids. Arabidopsis NPC2 and NPC6 are essential in gametogenesis, but their underlying role in the lipid remodeling remains elusive. Here, we show that these NPCs are required for triacylglycerol (TAG) production in pollen tube growth. NPC2 and NPC6 are highly expressed in developing pollen tubes and are localized at the endoplasmic reticulum. Mutants of NPC2 and NPC6 showed reduced rate of pollen germination, length of pollen tube and amount of lipid droplets (LDs). Overexpression of NPC2 or NPC6 induced LD accumulation, which suggests that these NPCs are involved in LD production. Furthermore, mutants defective in the biosynthesis of TAG, a major component of LDs, showed defective pollen tube growth. These results suggest that NPC2 and NPC6 are essential in gametogenesis for a role in hydrolyzing phospholipids and producing TAG required for pollen tube growth. Thus, lipid remodeling from phospholipids to TAG during pollen tube growth represents an emerging role for the NPC family in plant developmental control.
KIT mutations in mast cell tumours from cheetahs (Acinonyx jubatus) and domestic cats (Felis catus)
Authors: Tamlin Vanessa S. , Bottema Cynthia D. K. , Campbell‐Ward Michelle L. , Hanshaw Daren , Peaston Anne E.
Published: January 2021

Mast cell tumours (MCT) have been documented in numerous species and mutations within the KIT proto‐oncogene are implicated in the neoplastic biology of mast cells in humans, dogs and cats. This study determined high KIT gene nucleotide and Kit amino acid sequence homology between several species known to suffer mast cell neoplasia and especially high sequence conservation between the cheetah (Acinonyx jubatus) and domestic cat (Felis catus) KIT sequences. As a result, we hypothesised that KIT mutations would exist in the neoplastic DNA of four cheetahs diagnosed with MCT from a recent case series. PCR and Sanger sequencing identified conservative exon 6 KIT mutations in two of the four cheetahs. The mutations were different between the two cheetahs. Only wild‐type DNA in exons 6, 8, 9 and 11 of KIT was observed in the MCTs of the remaining two cheetahs. Twenty cutaneous MCTs from domestic cats were collected for KIT mutation comparison. Twelve tumours possessed a mutation within KIT exons 6, 8 or 9 (60%, 95% CI 38.5%‐81.5%). No mutations were detected in exon 11. There was no significant association between domestic feline MCT KIT mutation status and tumour histological grade (traditional schematic, P = .934; Sabattini 2‐tier schematic, P = .762) or mitotic index (P = .750). KIT mRNA and Kit protein sequences are conserved across species but the role of KIT in feline MCT pathogenesis is not completely understood.
Muscle myosin performance measured with a synthetic nanomachine reveals a class‐specific Ca2+‐sensitivity of the frog myosin II isoform
Authors: Pertici Irene , Bianchi Giulio , Bongini Lorenzo , Cojoc Dan , Taft Manuel H. , Manstein Dietmar J. , Lombardi Vincenzo , Bianco Pasquale
Published: January 2021

Key points

A nanomachine made of an ensemble of seven heavy‐meromyosin (HMM) fragments of muscle myosin interacting with an actin filament is able to mimic the half‐sarcomere generating steady force and constant‐velocity shortening.

To preserve Ca2+ as a free parameter, the Ca2+‐insensitive gelsolin fragment TL40 is used to attach the correctly oriented actin filament to the laser‐trapped bead acting as a force transducer.

The new method reveals that the performance of the nanomachine powered by myosin from frog hind‐limb muscles depends on [Ca2+], an effect mediated by a Ca2+‐binding site in the regulatory light chain of HMM. The Ca2+‐sensitivity is class‐specific because the performance of the nanomachine powered by mammalian skeletal muscle myosin is Ca2+ independent.

A model simulation is able to interface the nanomachine performance with that of the muscle of origin and provides a molecular explanation of the functional diversity of muscles with different orthologue isoforms of myosin.

An ensemble of seven heavy‐meromyosin (HMM) fragments of myosin‐II purified from the hindlimb muscles of the frog (Rana esculenta) is used to drive a synthetic nanomachine that pulls an actin filament in the absence of confounding effects of other sarcomeric proteins. In the present version of the nanomachine the +end of the actin filament is attached to the laser trapped bead via the Ca2+‐insensitive gelsolin fragment TL40, making [Ca2+] a free parameter. Frog myosin performance in 2 mm ATP is affected by Ca2+: in 0.1 mm Ca2+, the isometric steady force (F0, 15.25 pN) is increased by 50% (P = 0.004) with respect to that in Ca2+‐free solution, the maximum shortening velocity (V0, 4.6 μm s–1) is reduced by 27% (P = 0.46) and the maximum power (Pmax, 7.6 aW) is increased by 21% (P = 0.17). V0 reduction is not significant for the paucity of data at low force, although it is solidified by a similar decrease (33%, P < 0.0001) in the velocity of actin sliding as indicated by an in vitro motility assay (Vf). The rate of ATP‐hydrolysis in solution (φ) exhibits a similar calcium dependence. Ca2+ titration curves for Vf and φ give Kd values of ∼30 μm. All the above mechanical and kinetic parameters are independent of Ca2+ when HMM from rabbit psoas myosin is used, indicating that the Ca2+‐sensitivity is a class‐specific property of muscle myosin. A unique multiscale model allows interfacing of the nanomachine performance to that of the muscle of origin and identifies the kinetic steps responsible for the Ca2+‐sensitivity of frog myosin.
Effect of ambient temperature on respiratory tract cells exposed to SARS-CoV-2 viral mimicking nanospheres—An experimental study
Authors: Kumar Sachin , Paul Alexandra , Chatterjee Sayantan , Pütz Sabine , Nehra Natasha , Wang Daniel S. , Nisar Arsalan , M. Jennings Christian , Parekh Sapun H.
Published: January 2021

The novel coronavirus caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has reached more than 160 countries and has been declared a pandemic. SARS-CoV-2 infects host cells by binding to the angiotensin-converting enzyme 2 (ACE-2) surface receptor via the spike (S) receptor-binding protein (RBD) on the virus envelope. Global data on a similar infectious disease spread by SARS-CoV-1 in 2002 indicated improved stability of the virus at lower temperatures facilitating its high transmission in the community during colder months (December–February). Seasonal viral transmissions are strongly modulated by temperatures, which can impact viral trafficking into host cells; however, an experimental study of temperature-dependent activity of SARS-CoV-2 is still lacking. We mimicked SARS-CoV-2 with polymer beads coated with the SARS-CoV-2 S protein to study the effect of seasonal temperatures on the binding of virus-mimicking nanospheres to lung epithelia. The presence of the S protein RBD on nanosphere surfaces led to binding by Calu-3 airway epithelial cells via the ACE-2 receptor. Calu-3 and control fibroblast cells with S-RBD-coated nanospheres were incubated at 33 and 37 °C to mimic temperature fluctuations in the host respiratory tract, and we found no temperature dependence in contrast to nonspecific binding of bovine serum ablumin-coated nanospheres. Moreover, the ambient temperature changes from 4 to 40 °C had no effect on S-RBD-ACE-2 ligand-receptor binding and minimal effect on the S-RBD protein structure (up to 40 °C), though protein denaturing occurred at 51 °C. Our results suggest that ambient temperatures from 4 to 40 °C have little effect on the SARS-CoV-2-ACE-2 interaction in agreement with the infection data currently reported.
Preferential sputtering of metal oxide mixture thin films
Authors: Mende Mathias , Carstens Florian , Ehlers Henrik , Ristau Detlev
Published: January 2021

Metal oxide mixture materials enable the production of dielectric multilayer coatings for highest power laser applications. During thin film deposition, when using sputtering techniques in combination with composite target materials, preferential sputtering occurs on the target surface. The quantitative analysis of the mixture thin film composition, usually performed by ion beam based depth profiling methods, is also affected by preferential sputtering. To gain a deeper understanding, the atomic composition variation of sputtered mixture material surfaces is calculated applying the Monte Carlo simulation program tridyn. The simulation results are compared to the atomic composition gradient measured via depth profiling x-ray photoelectron spectroscopy for mixture thin films composed of HfO2, Sc2O3, Al2O3, and SiO2. The deviations between the experimental and simulated data are discussed with respect to the different mixture material combinations.
Vaccinemakers ponder how to adapt to virus variants
Authors: Kupferschmidt Kai
Published: January 2021

Moderna aims to develop booster shot to counter mutations.
Expansion sequencing: Spatially precise in situ transcriptomics in intact biological systems
Authors: Alon Shahar , Goodwin Daniel R. , Sinha Anubhav , Wassie Asmamaw T. , Chen Fei , Daugharthy Evan R. , Bando Yosuke , Kajita Atsushi , Xue Andrew G. , Marrett Karl , Prior Robert , Cui Yi , Payne Andrew C. , Yao Chun-Chen , Suk Ho-Jun , Wang Ru , Yu Chih-Chieh (Jay) , Tillberg Paul , Reginato Paul , Pak Nikita , Liu Songlei , Punthambaker Sukanya , Iyer Eswar P. R. , Kohman Richie E. , Miller Jeremy A. , Lein Ed S. , Lako Ana , Cullen Nicole , Rodig Scott , Helvie Karla , Abravanel Daniel L. , Wagle Nikhil , Johnson Bruce E. , Klughammer Johanna , Slyper Michal , Waldman Julia , Jané-Valbuena Judit , Rozenblatt-Rosen Orit , Regev Aviv ,   IMAXT Consortium, Church George M. , Marblestone Adam H. , Boyden Edward S. , Ali H. R. , Al Sa’d M. , Alon S. , Aparicio S. , Battistoni G. , Balasubramanian S. , Becker R. , Bodenmiller B. , Boyden E. S. , Bressan D. , Bruna A. , Burger Marcel , Caldas C. , Callari M. , Cannell I. G. , Casbolt H. , Chornay N. , Cui Y. , Dariush A. , Dinh K. , Emenari A. , Eyal-Lubling Y. , Fan J. , Fatemi A. , Fisher E. , González-Solares E. A. , González-Fernández C. , Goodwin D. , Greenwood W. , Grimaldi F. , Hannon G. J. , Harris O. , Harris S. , Jauset C. , Joyce J. A. , Karagiannis E. D. , Kovačević T. , Kuett L. , Kunes R. , Küpcü Yoldaş A. , Lai D. , Laks E. , Lee H. , Lee M. , Lerda G. , Li Y. , McPherson A. , Millar N. , Mulvey C. M. , Nugent F. , O'Flanagan C. H. , Paez-Ribes M. , Pearsall I. , Qosaj F. , Roth A. J. , Rueda O. M. , Ruiz T. , Sawicka K. , Sepúlveda L. A. , Shah S. P. , Shea A. , Sinha A. , Smith A. , Tavaré S. , Tietscher S. , Vázquez-García I. , Vogl S. L. , Walton N. A. , Wassie A. T. , Watson S. S. , Weselak J. , Wild S. A. , Williams E. , Windhager J. , Whitmarsh T. , Xia C. , Zheng P. , Zhuang X.
Published: January 2021

Identifying transcript location in cells

Identifying where specific RNAs occur within a cell or tissue has been limited by technology and imaging capabilities. Expansion microscopy has allowed for better visualization of small structures by expanding the tissues with a polymer- and hydrogel-based system. Alon
et al.
combined expansion microscopy with long-read in situ RNA sequencing, resulting in a more precise visualization of the location of specific transcripts. This method, termed “ExSeq” for expansion sequencing, was used to detect RNAs, both new transcripts and those previously demonstrated to localize to neuronal dendrites. Unlike other in situ sequencing methods, ExSeq does not target sets of genes. This technology thus unites spatial resolution, multiplexing, and an unbiased approach to reveal insights into RNA localization and its physiological roles in developing and active tissue.

Science
, this issue p.
eaax2656
MAIT cell activation augments adenovirus vector vaccine immunogenicity
Authors: Provine Nicholas M. , Amini Ali , Garner Lucy C. , Spencer Alexandra J. , Dold Christina , Hutchings Claire , Silva Reyes Laura , FitzPatrick Michael E. B. , Chinnakannan Senthil , Oguti Blanche , Raymond Meriel , Ulaszewska Marta , Troise Fulvia , Sharpe Hannah , Morgan Sophie B. , Hinks Timothy S. C. , Lambe Teresa , Capone Stefania , Folgori Antonella , Barnes Eleanor , Rollier Christine S. , Pollard Andrew J. , Klenerman Paul
Published: January 2021

Vaccines get a help-MAIT

Mucosal-associated invariant T (MAIT) cells are a T cell subset important for mucosal homeostasis. These cells recognize derivatives of microbiota-derived vitamin B2 precursors but can also be activated by certain cytokines in the context of viral infections. Provine
et al.
report that a leading adenoviral vector vaccine, ChAdOx1, activated MAIT cells in immunized mice (see the Perspective by Juno and O'Connor). This activation required interferon-α produced by plasmacytoid dendritic cells as well as monocyte-derived interleukin-18 and tumor necrosis factor. MAIT cell activation positively correlated with vaccine-mediated T cell responses in human subjects, and mice deficient in MAIT cells showed impaired CD8
+
T cell immunity to target antigens after vaccination. This work suggests an additional pathway that could be exploited to enhance the efficacy of vaccines.

Science
, this issue p.
521
; see also p.
460
Unipolar stroke, electroosmotic pump carbon nanotube yarn muscles
Authors: Chu Hetao , Hu Xinghao , Wang Zhong , Mu Jiuke , Li Na , Zhou Xiaoshuang , Fang Shaoli , Haines Carter S. , Park Jong Woo , Qin Si , Yuan Ningyi , Xu Jiang , Tawfick Sameh , Kim Hyungjun , Conlin Patrick , Cho Maenghyo , Cho Kyeongjae , Oh Jiyoung , Nielsen Steven , Alberto Kevin A. , Razal Joselito M. , Foroughi Javad , Spinks Geoffrey M. , Kim Seon Jeong , Ding Jianning , Leng Jinsong , Baughman Ray H.
Published: January 2021

Pump it up

Carbon nanotube yarns can be used as electrochemical actuators because infiltration with ions causes a contraction in length and an expansion in diameter. Either positive or negative ions can cause this effect. Chu
et al.
constructed an all-solid-state muscle that eliminated the need for an electrolyte bath, which may expand the potential for its use in applications. By infiltrating the yarns with charged polymers, the fibers start partially swollen, so the length can increase through the loss of ions. It is thus possible to increase the overall stroke of the muscle. Further, these composite materials show a surprising increase in stroke with scan rate.

Science
, this issue p.
494
Early plant organics increased global terrestrial mud deposition through enhanced flocculation
Authors: Zeichner Sarah S. , Nghiem Justin , Lamb Michael P. , Takashima Nina , de Leeuw Jan , Ganti Vamsi , Fischer Woodward W.
Published: January 2021

What matters for mudrocks

Rock such as slate and shale, which form from mud, suddenly start appearing in the geologic record around 450 million years ago. Their appearance at about the same time as certain plants seems to implicate plant roots in the formation of these ubiquitous rocks. Zeichner
et al.
found a different route for creating the flocculation required for mudrock. Using analog experiments, the authors found that organic matter from plants alone was sufficient for the formation of flocs—aggregates of small silt and clay particles—which are required to deposit mudrock. This observation could explain the appearance of these rocks in places where the plants did not have deep roots.

Science
, this issue p.
526
Sub-7-femtosecond conical-intersection dynamics probed at the carbon K-edge
Authors: Zinchenko Kristina S. , Ardana-Lamas Fernando , Seidu Issaka , Neville Simon P. , van der Veen Joscelyn , Lanfaloni Valentina Utrio , Schuurman Michael S. , Wörner Hans Jakob
Published: January 2021

How fast is electronic relaxation?

Technical advances in extending spectroscopy to the attosecond time scale has caused considerable interest in experimental studies of various ultrafast processes that were previously inaccessible. Using attosecond transient absorption around the carbon K-edge accompanied by ab initio quantum dynamics simulations, Zinchenko
et al.
investigated ultrafast, non-adiabatic dynamics in the ethylene cation. They directly observed the electronic D
1
→ D
0
relaxation mediated by the conical intersection taking place within 7 femtoseconds, far shorter than any vibrational period or any previously reported electronic relaxation. The demonstrated technique is directly applicable to liquids and solutions, enabling further studies of charge- and energy-transfer dynamics of organic molecules in chemical and biochemical systems.

Science
, this issue p.
489
Merging shuttle reactions and paired electrolysis for reversible vicinal dihalogenations
Authors: Dong Xichang , Roeckl Johannes L. , Waldvogel Siegfried R. , Morandi Bill
Published: January 2021

Shuttling halide pairs back and forth

The transfer of adjacent hydrogens from a saturated to an unsaturated organic compound is a fairly common reaction. However, analogs that shuttle two heavy atoms back and forth are much harder to catalyze. Dong
et al.
report an electrochemical approach that transfers a pair of adjacent chlorines or bromines from an alkyl compound to an olefin. The method could help to remediate halogenated pollutants while concurrently producing fine chemicals.

Science
, this issue p.
507
Insights from SARS-CoV-2 sequences
Authors: Martin Michael A. , VanInsberghe David , Koelle Katia
Published: January 2021

Analysis of viral sequences can tell us how SARS-CoV-2 spreads and adapts
Lessons in antiviral immunity
Authors: Hope Jennifer L. , Bradley Linda M.
Published: January 2021

Immune responses to SARS-CoV-2 reveal regulation and dynamics of lymphocytes
Caring for critically ill adults in paediatric intensive care units in England during the COVID-19 pandemic: planning, implementation and lessons for the future
Authors: Sinha Ruchi , Aramburo Angela , Deep Akash , Bould Emma-Jane , Buckley Hannah L , Draper Elizabeth S , Feltbower Richard , Mitting Rebecca , Mahoney Sarah , Alexander John , Playfor Stephen , Chan-Dominy Amy , Nadel Simon , Suntharalingam Ganesh , Fraser James , Ramnarayan Padmanabhan
Published: January 2021

Objective

To describe the experience of paediatric intensive care units (PICUs) in England that repurposed their units, equipment and staff to care for critically ill adults during the first wave of the COVID-19 pandemic.

Design

Descriptive study.

Setting

Seven PICUs in England.

Main outcome measures

(1) Modelling using historical Paediatric Intensive Care Audit Network data; (2) space, staff, equipment, clinical care, communication and governance considerations during repurposing of PICUs; (3) characteristics, interventions and outcomes of adults cared for in repurposed PICUs.

Results

Seven English PICUs, accounting for 137 beds, repurposed their space, staff and equipment to admit critically ill adults. Neighbouring PICUs increased their bed capacity to maintain overall bed numbers for children, which was informed by historical data modelling (median 280–307 PICU beds were required in England from March to June). A total of 145 adult patients (median age 50–62 years) were cared for in repurposed PICUs (1553 bed-days). The vast majority of patients had COVID-19 (109/145, 75%); the majority required invasive ventilation (91/109, 85%). Nearly, a third of patients (42/145, 29%) underwent a tracheostomy. Renal replacement therapy was provided in 20/145 (14%) patients. Twenty adults died in PICU (14%).

Conclusion

In a rapid and unprecedented effort during the first wave of the COVID-19 pandemic, seven PICUs in England were repurposed to care for adult patients. The success of this effort was underpinned by extensive local preparation, close collaboration with adult intensivists and careful national planning to safeguard paediatric critical care capacity.
Hyperthermic intraperitoneal chemotherapy (HIPEC) as another treatment modality for desmoplastic round cell tumour patients: first paediatric experience from UK
Authors: Sjoberg Bexelius Tomas , Chisholm Julia C , Okoye Bruce , Cecil Tom , Angelini Paola , Dayal Sanjeev
Published: January 2021

We present the first young paediatric patient with desmoplastic small round cell tumour (DSRCT) treated in UK with hyperthermic intraperitoneal chemotherapy (HIPEC). A 7-year-old girl was diagnosed with abdominal DSRCT with peritoneal and liver metastases. After six cycles of chemotherapy she obtained a partial response, including almost complete resolution of the two liver metastases. It was decided to pursue cytoreductive surgery (CRS) combined with HIPEC, a procedure commonly performed in adults, but seldom in a child. The surgery was macroscopically complete and the HIPEC uncomplicated. She continued treatment without delays, including whole abdomino-pelvic radiotherapy and maintenance chemotherapy (cyclophosphamide/vinorelbine for 12 months). She is currently in complete remission 4 months after end of treatment and 26 months after diagnosis. HIPEC was made possible by successful collaboration between multiple teams. CRS-HIPEC proved to be safe and feasible and could be offered to other children with diagnoses of peritoneal malignancies across the UK.
Mediastinal FDG-positive lymph nodes simulating melanoma progression: drug-induced sarcoidosis like/lymphadenopathy related to ipilimumab
Authors: González-Cruz Carlos , Bodet Domingo , Muñoz-Couselo Eva , García-Patos Vicente
Published: January 2021

Drug-induced sarcoidosis-like reactions (DISRs) are systemic granulomatous diseases that develop in the context of a new drug onset. Ipilimumab is an immune checkpoint inhibitor (ICI) approved for the treatment of advanced melanoma which has been associated with DISR. Differential diagnosis between tumour progression and DISR by positron emission tomography/computed tomography (PET/CT) in patients treated with an ICI can be a challenge. A 31-year-old woman was diagnosed with a stage IIIB melanoma in her back. Ipilimumab 10 mg/kg was initiated. After 1 month of finishing the treatment a routine, PET/CT showed multiple enlarged mediastinal and hilar lymph nodes FDG-positive. A transbronchial biopsy showed sarcoid-like granulomatous infiltration which favoured the diagnosis of DISR related to ipilimumab. The patient remained asymptomatic and lymphadenopathy regressed progressively after 11 months. Our work highlights the importance of differentiating DISR from tumour progression, before unnecessary changes in therapeutic strategies. PET/CT is a useful diagnostic tool for its follow-up.
De Garengeot’s hernia in an elderly woman as a diagnostic challenge: a review of literature
Authors: Ahmed Zeeshan Saboor , Azam Sufyan , Shenton Ayeshea , Akingboye Akinfemi Ayobami
Published: January 2021

De Garengeot’s hernia is the presence of an appendix in a femoral hernia and can be a rare cause of an acute groin swelling. Here, we present a case report of an elderly woman who was referred to us with a short history of a painful, tender lump in the right groin associated with nausea and vomiting. Her inflammatory markers were raised, and to establish a final diagnosis, an urgent CT scan was requested which showed a blind ending tubular structure in a hernia sac. She was taken to the theatre for urgent exploration of the groin which revealed that it was a femoral hernia, the sac of which contained gangrenous appendix, the base of which could not be accessed through the groin incision and, therefore, a lower midline laparotomy incision was made and a formal appendicectomy was done.
Anaemia secondary toEscherichia colimycotic aneurysm
Authors: Wong Zhi Wan , Ong Kevin
Published: January 2021

Mycotic aneurysms can pose a diagnostic dilemma due to their variable presentations. We present a case of a 93-year-old man initially presenting with fevers, intermittent chest pain and normocytic anaemia refractory to repeated blood transfusions. He received intravenous ceftriaxone asEscherichia coligrew in his blood cultures. His chest X-ray showed a widened mediastinum. A subsequent CT of the chest discovered a mycotic aneurysm at the descending thoracic aorta. He had a good outcome and was thriving after 1 year post endovascular repair.
Monophasic spindle cell myxoid synovial sarcoma of the hand: promising results with marginal resection
Authors: Vijayan Sandeep , Mohammed Afsal P , Kulkarni Mahesh Suresh , Rao Sharath Kumar
Published: January 2021

Synovial sarcomas are deep-seated, genetically distinct, malignant neoplasms seen in young adults, with a male preponderance. They have unusual clinical and pathological presentation and mimic many other sarcomas and carcinomas, making the diagnosis quite challenging. Although four variants are identified, occurrence in the hand is extremely rare and leads to significant morbidity. There is a high incidence of local recurrence and distant metastasis within the first 2 years. We report the case of an elderly woman with monophasic spindle cell synovial sarcoma who presented with painless swelling in her palm and underwent local excision of the neoplasm. At 2-year follow-up, she remains totally asymptomatic with normal function of the hand. We also attempt to give an overview about monophasic spindle cell synovial sarcoma with the differentials, which would help surgeons in prompt diagnosis and appropriate management.
Reinforcing the vascular disruption theory of the genesis of Poland’s syndrome: a rare association of diaphragmatic eventration in a preterm infant with severe musculoskeletal defects
Authors: Shahrul Baharin Nadira , Awadh Hashim Eman , Bin Huey Quek , Chandran Suresh
Published: January 2021

A preterm female infant was admitted at birth with respiratory distress. On examination, she had an asymmetric right chest wall and ipsilateral small hand. Air entry was reduced over the right chest. A clinical diagnosis of Poland’s syndrome was made based on the hypoplasia of the right pectoral muscles, absent nipple, deformed ribs and symbrachydactyly of the ipsilateral hand. Chest X-ray suggested and ultrasound confirmed eventration of the right hemidiaphragm. ‘Subclavian artery supply disruption sequence’ (SASDS) theory by Bavnick and Weaver remains the most accepted pathogenic mechanism in Poland’s syndrome. This case reinforces SASDS theory associated with the genesis of Poland’s syndrome that relates to the pathogenicity of vascular disruption of subclavian artery, characteristics of which are unilateral pectoral defects, symbrachydactyly and eventration of the diaphragm. At 2 months, she underwent diaphragm plication. She is under review by our multidisciplinary surgical team for reconstruction of the chest deformity.
Concurrent development of HIV-negative Kaposi’s sarcoma and mycosis fungoides in an elderly Inuit from Canada
Authors: Bedier Helbies , Lin John , Julien Louis-André , Routy Jean-Pierre
Published: January 2021

An 88-year-old Inuit man from Northern Canada presented with an extensive skin rash associated with numerous violaceous skin nodules on his palms and lower extremities. Biopsy of a skin nodule revealed Kaposi’s sarcoma (KS), a human herpesvirus 8 (HHV8)-associated malignancy, whereas biopsy of the erythematous skin showed an atypical infiltrate of CD4-positive T-cells that, together with TCR gene rearrangement and presence of clonal T-cells in peripheral blood by flow cytometry, was consistent with a T-cell lymphoma, mycosis fungoides (MF) subtype. Serology was negative for HIV and HTLV-I/II and no immunodeficiency syndrome was identified. The patient was successfully treated with an oral retinoid for KS, and with topical hydrocortisone and ultraviolet B (UVB) phototherapy for MF. This case highlights the existence of HHV8-related lesions in native persons of Northern Canada, and also that MF-induced immunosuppression combined with immunosenescence may play a role in the development of non-HIV-related KS.
Extranodal blastoid/pleomorphic variant of mantle cell lymphoma involving the testis and skin
Authors: Anusim Nwabundo , Gupta Alia , Howard George , Jaiyesimi Ishmael
Published: January 2021

We report a case of extranodal mantle cell lymphoma of the testis in a 72-year-old Caucasian man who presented to his physician’s office with rapidly enlarging left testicular mass and skin lesions which were subsequently biopsy-proven to be mantle cell lymphoma. We discuss the clinicopathological features and current management in relapsed and refractory settings of this rare presentation of mantle cell lymphoma.
Central serous chorioretinopathy secondary to solar retinopathy: an unusual presentation
Authors: Rathore Priyanka , Singh Anju
Published: January 2021

Solar retinopathy (SR) results from unprotected solar eclipse viewing and also from gazing at the sun for a long duration. It has been known for a long that direct viewing of the sun causes visual disruption. Usually, there is a disruption of the inner segment–outer segment junction, but an association of central serous chorioretinopathy (CSCR) with SR is quite rare. We report a case of CSCR associated with solar eclipse viewing.
Community-level spillover effects of an intervention to prevent intimate partner violence and HIV transmission in rural Ethiopia
Authors: Leight Jessica , Deyessa Negussie , Verani Fabio , Tewolde Samuel , Sharma Vandana
Published: January 2021

Background

Intimate partner violence (IPV) is associated with adverse health and psychosocial outcomes. We analysed the spillover effects of Unite for a Better Life (UBL), an intervention evaluated in a cluster randomised controlled trial using a double-randomised design; previous evidence suggests UBL reduced IPV in rural Ethiopia among direct beneficiaries.

Methods

Villages (n=64) were randomly allocated to control, or to receive UBL delivered to men, women or couples. Each cluster comprised 106 surveyed households, including 21 randomly selected indirect beneficiary households who were not included in the intervention. Primary and secondary IPV outcomes included women’s experience and men’s perpetration of past-year physical or sexual IPV 24 months postintervention. An intention-to-treat analysis was conducted comparing indirect beneficiaries to sampled households in control communities. The analysis includes 2516 households surveyed at baseline in 2014–2015 (1680 households in the control arm, 258 indirect beneficiary households in the couples’ arm, 287 indirect beneficiary households in the women’s arm and 291 indirect beneficiary households in the men’s arm). Follow-up data were available from 88% of baseline respondents and 86% of baseline spouses surveyed in 2017–2018, a total of 4379 individuals.

Results

Among indirect beneficiaries, there was no statistically significant intervention effect on women’s past-year experience of physical or sexual IPV, while men’s UBL significantly reduced reported perpetration of past-year sexual IPV (Adjusted Odds Ratio: 0.55; 95% CI 0.38 to 0.80, p=0.002). The intervention effects among indirect beneficiaries were statistically similar to those reported for the direct beneficiaries. In general, the hypothesis of equal effects cannot be rejected.

Conclusion

A gender-transformative intervention delivered to men was effective in reducing reported IPV even among indirect beneficiaries, suggesting that the programme had positive spillover effects in diffusing information and changing behaviours within the broader community.

Trial registration numbers

NCT02311699and American Economic Association Registry (AEARCTR-0000211).