bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of ERβ induces bovine ovarian granulosa cell autophagy via the AKT/mTOR pathway
Authors: Liu Guangyu , Zheng Yuxin , Gao Huimin , Cui Wenfei , Zhao Fan , Liu Ning , Tang Xiaorong , Jiang Zhongliang
Published: May 2022

The aim of our study was to determine whether silencing or overexpression of estrogen receptor β (ERβ) regulates cell proliferation, steroidogenesis, autophagy and signalling pathways in bovine ovarian granulosa cells in vitro. In this study, bovine ovarian granulosa cells (BGCs) were cultured and transfected with ERβ siRNA (si‐ERβ) or a plasmid overexpressing ERβ (oe‐ERβ), and CCK‐8 kit was used to assess cell proliferation. Real‐time PCR was used to measure gene transcription. Western blotting was used to measure protein expression, and a specific kit was used to measure the production of steroid hormones. The results showed the expression level of ERβ affects BGC proliferation according to the gene transcription levels of FSHR, CYP19A1, HSD3β1 and STAR and the production of E2 and P4. ERβ was identified as an important nuclear receptor that induced BGC autophagy based on the mRNA and protein expression of autophagy‐related genes. Furthermore, the role of ERβ in BGC autophagy was confirmed through treatment with rapamycin (RAPA) or 3‐methyladenine (3‐MA) in BGCs by cotransfection with si‐ERβ or oe‐ERβ in BGCs. The results related to AKT/mTOR signalling and phosphorylation suggested that ERβ induces BGC autophagy through attenuating AKT/mTOR signalling. In summary, this study demonstrates that silencing or overexpression of ERβ regulates BGC proliferation and function and induces BGC autophagy by targeting AKT/mTOR signalling. These data reveal a novel regulatory mechanism of autophagy via ERβ and provide insights into the role of autophagy in BGCs.
Hamstring muscle activation strategies during eccentric contractions are related to the distribution of muscle damage
Authors: Goreau Valentin , Pigne Robin , Bernier Nathan , Nordez Antoine , Hug François , Lacourpaille Lilian
Published: May 2022

Large inter‐individual variability of activation strategies is observed during hamstring strengthening exercises but their consequences remain unexplored. The objective of this study was to determine whether individual activation strategies are related to the distribution of damage across the hamstring muscle heads semimembranosus (SM), semitendinosus (ST), and biceps femoris (BF) after eccentric contractions. 24 participants performed 5 sets of 15 maximal eccentric contractions of knee flexors on a dynamometer, while activation of each muscle head was assessed using surface electromyography. Knee flexion maximal isometric strength was assessed before exercise and 48 h afterward. Shear modulus was measured using shear wave elastography before exercise and 30 min afterward to quantify the distribution of damage across the hamstring muscle heads. At 48 h, maximal knee flexion torque had decreased by 15.9% ± 16.9% (p < 0.001). Although no differences between activation ratios of each muscle were found during the eccentric exercise (all p > 0.364), we reported a heterogeneous distribution of damage, with a larger change in shear modulus of ST/Hams than SM/Hams (+70.8%, p < 0.001) or BF/Hams (+50.3%, p < 0.001). A large correlation was found between the distribution of activation and the distribution of damage for ST/Hams (r = 0.69; p < 001). This study provides evidence that the distribution of activation during maximal eccentric contractions has mechanical consequences for synergist muscles. Further studies are needed to understand whether individual activation strategies influence the distribution of structural adaptations after a training program.
The effect of planning time on penultimate and ultimate step kinematics and subsequent knee moments during sidestepping
Authors: Byrne Sean , Lay Brendan , Staynor Jonathan , Alderson Jacqueline , Donnelly Cyril J.
Published: May 2022

Frontal plane postures during the ultimate step of sidestepping are linked to increased anterior cruciate ligament injury risk. However, there is a lack of research detailing the kinematic strategies present in the penultimate step. This study, therefore, investigated penultimate and ultimate step kinematics of planned sidestepping (pSS) and unplanned sidestepping (upSS) to further understand the effect of planning time on known ultimate step kinematic and kinetic differences. Sixty male amateur Australian Rules football players performed three trials of straight‐line running (RUN), pSS, and upSS in a randomized order. Mediolateral foot placement and three‐dimensional joint kinematics for the knee, pelvis, and trunk were measured at final foot contact of the penultimate step and initial foot contact of the ultimate step. Peak knee moments were measured during the weight acceptance phase of the ultimate step. In pSS, at the penultimate step final foot contact, the support foot was placed across the midline of the center of mass, in the frontal plane, contralateral to the sidestep direction. Greater trunk lateral flexion toward the sidestep direction and greater negative pelvic lateral tilt were observed in pSS compared with upSS and RUN. Differences between pSS and upSS frontal plane kinematics at penultimate step final foot contact suggest preparatory reorientation strategies are likely constrained by the amount of planning time available. As there are clear differences in preparatory kinematics, we recommend that planning time be considered when training and assessing sidestepping maneuvers and planned and unplanned maneuvers not be treated as interchangeable skills.
A retrospective analysis of all‐cause and cause‐specific mortality rates in French male professional footballers
Authors: Orhant Emmanuel , Carling Christopher , Chapellier Jean‐François , Marchand Jean‐Luc , Pradat Pierre‐François , Elbaz Alexis , Maniez Sandrine , Moisan Frédéric , Rochcongar Pierre
Published: May 2022

This study retrospectively compared all‐cause and cause‐specific mortality in French male professional football players with data from France's national population. Altogether, 6114 individuals born in Metropolitan France or in one of its overseas territories who played at least one competitive match in France's professional football championships between January 1, 1968 and December 31, 2015, were identified and followed up for vital status obtained from a national reference database until December 31, 2015. Data on all‐cause and cause‐specific mortality were subsequently compared to the expected number of deaths for the national population after standardization for the year, age, and sex. Ratios between observed and expected deaths provided standardized mortality ratios (SMR) along with 95% confidence intervals (95% CI). Linear trends were investigated using the Poisson trend test. Altogether, 662 player deaths were observed. All‐cause mortality overall was lower than that of the national population (SMR: 0.69, 95% CI 0.64–0.75). An excess of deaths from dementia was observed in the players (SMR: 3.38, 95% CI: 2.49–4.50) whereas mortality from diseases of the nervous (SMR: 0.64, 95% CI: 0.35–1.08) and cardiovascular systems (SMR: 0.82, 95% CI: 0.70–0.96), and cancer (SMR: 0.67, 95% CI: 0.58–0.76) was lower. Lower overall mortality and that owing to common cardiovascular and cancer‐related diseases were reported in French professional football players compared to France's national population. In line with previous studies, however, excess mortality from dementia was observed in the players. Career length was not associated with all‐cause or cause‐specific mortality. Prospective matched‐cohort studies are necessary to identify the neurologic impact of participation in professional football.
FLCSS: A fuzzy‐based longest common subsequence method for uncertainty management in trajectory similarity measures
Authors: Boroumand Faraz , Alesheikh Ali Asghar , Sharif Mohammad , Farnaghi Mahdi
Published: May 2022

The large quantity of movement data collected from various sources can be inherently uncertain and heterogeneous. In the movement data analysis and mining spectrum, computing the similarity of trajectories while considering the uncertainty and heterogeneity has been less addressed. Generally, two factors of sampling and positioning error cause uncertainty in trajectory databases. Therefore, in this research, a method based on the longest common subsequence (LCSS), named FLCSS, is proposed that uses fuzzy theory and the bead model to consider the uncertainty of trajectories originated from positioning and sampling errors. The performance of FLCSS is evaluated by implementations on real and synthetic datasets, and compared with six important and commonly used similarity measurement methods, namely, LCSS, edit distance on real sequence (EDR), dynamic time warping (DTW), edit distance with real penalty (ERP), Hausdorff distance (HD), and Fréchet distance (FD). The results show that FLCSS has a better performance compared to other methods, in terms of sensitivity to point displacement, noise, and different sampling rates. Furthermore, the high correlation between FLCSS and LCSS (ρ = 0.91) confirms the robustness of the proposed method in considering uncertainty in the trajectory databases.
A physiology‐based trigger score to guide perioperative transfusion of allogeneic red blood cells: A multicentre randomised controlled trial
Authors: Lu Kejian , Huang Zehan , Liang Shucong , Pan Fengting , Zhang Chunying , Wei Jingqing , Wei Huijun , Wang Yafeng , Liao Ren , Huang Ailan , Huang Yanjuan
Published: May 2022

Background

Restrictive blood transfusion is recommended by major guidelines for perioperative management, but requires objective assessment at 7–10 g/dl haemoglobin (Hb). A scoring system that considers the physiological needs of the heart may simply the practice and reduce transfusion.

Methods

Patients (14–65 years of age) undergoing non‐cardiac surgery were randomised at a 1:1 ratio to a control group versus a Perioperative Transfusion Trigger Score (POTTS) group. POTTS (maximum of 10) was calculated as 6 plus the following: adrenaline infusion rate (0 for no infusion, 1 for ≤0.05 μg·kg−1·min−1, and 2 for higher rate), FiO2 to keep SpO2 at ≥95% (0 for ≤35%, 1 for 36%–50%, and 2 for higher), core temperature (0 for <38°C, 1 for 38–40°C, and 2 for higher), and angina history (0 for no, 1 for exertional, and 2 for resting). Transfusion is indicated when actual Hb is lower than the calculated POTTS in individual patients. Transfusion in the control group was based on the 2012 American Association for Blood Banks (AABB) guideline. The primary outcome was the proportion of the patients requiring transfusion of allogeneic red blood cells (RBCs) during the perioperative period (until discharge from hospital), as assessed in the intention‐to‐treat (ITT) population (all randomised subjects).

Result

A total of 864 patients (mean age 44.4 years, 244 men and 620 women) were enrolled from December 2017 to January 2021 (433 in the control and 431 in the POTTS group). Baseline Hb was 9.2 ± 1.8 and 9.2 ± 1.7 g/dl in the control and POTTS groups, respectively. In the ITT analysis, the proportion of the patients receiving allogeneic RBCs was 43.9% (190/433) in the control group versus 36.9% (159/431) in the POTTS group (p = 0.036). Lower rate of allogeneic RBCs transfusion in the POTTS group was also evident in the per‐protocol analysis (42.8% vs. 35.5%, p = 0.030). Transfusion volume was 4.0 (2.0, 6.0) and 3.5 (2.0, 5.5) units (200 ml/unit) in the control and POTTS groups, respectively (p = 0.25). The rate of severe postoperative complications (Clavien‐Dindo grade IIIa and higher) was 3.9% in the control group versus 1.2% in the POTTS group (p = 0.010).

Conclusion

Transfusion of allogeneic RBCs based on the POTTS was safe and reduced the transfusion requirement in patients undergoing non‐cardiac surgery.
Incisor enamel microstructure places New and Old World Eomyidae outside Geomorpha (Rodentia, Mammalia)
Authors: Kalthoff Daniela C. , Fejfar Oldrich , Kimura Yuri , Bailey Bruce E. , Mörs Thomas
Published: May 2022

The lower incisor enamel microstructure of the fossil rodent family Eomyidae was believed to be three‐layered and highly derived but rather uniform throughout the clade. Here, we describe a new four‐layered schmelzmuster in Eomyidae consisting of a three‐fold portio interna with longitudinal oriented, uniserial Hunter‐Schreger bands and a one‐fold portio externa, accounting for a unique enamel microstructure character combination in Rodentia. This new schmelzmuster type has developed early in eomyid evolution and is detectable already in the late Eocene (Chadronian) of North America. In European eomyids, it first occurs in the early Miocene (MN 3), implying that this four‐layered schmelzmuster was not present in all members of the family but restricted to species included in Eomyini and some genera currently considered Eomyidae incertae sedis within Eomyidae. Additionally, our analysis recognizes three taxa with schmelzmuster divergent from all other eomyids. Incisor enamel microstructure does not advocate a close phylogenetic relationship of Eomyidae to either fossil or extant Heteromyidae and Geomyidae, nor to fossil Heliscomyidae and Florentiamyidae. Our results rather support the view that Eomyidae are placed outside Geomorpha.
Design a Multifunctional Soft Tactile Sensor Enhanced by Machine Learning Approaches
Authors: Yang Wu-Te , Tomizuka Masayoshi
Published: May 2022

Tactile sensors are essential to robot hands that deal with various objects and interact with the environment. Soft tactile sensors are especially important to capture tactile information about delicate, irregular-shaped, or unknown objects. This paper introduces a soft tactile sensor that can simultaneously estimate the contact force, contact feature, and contact point. Inspired by multifunctional human skin, the proposed design has a dual-layer structure and is multifunctional. The top layer consists of a group of sensing elements that detect the contact location and contact feature enhanced by the bagging classifier based on the k-nearest neighbors. The sensor elements were biomimetically and analytically designed as a pyramid shape that mimicked the mountain ridge-like structure in human skin to improve sensitivity. The bottom layer was made by a piece of Velostat sandwiched between conductive fabrics that can measure the contact force. The relationship between the sensing voltage and the contact force was modeled by the Nadaraya–Watson regressor. The performance of the proposed sensor was verified by a repeatability test. Furthermore, we demonstrated the effectiveness of the proposed sensor on a robotic gripper. The experimental results show that this sensor is able to detect contact information of fragile objects.
FOXG1 sequentially orchestrates subtype specification of postmitotic cortical projection neurons
Authors: Liu Junhua , Yang Mengjie , Su Mingzhao , Liu Bin , Zhou Kaixing , Sun Congli , Ba Ru , Yu Baocong , Zhang Baoshen , Zhang Zhe , Fan Wenxin , Wang Kun , Zhong Min , Han Junhai , Zhao Chunjie
Published: May 2022

The mammalian neocortex is a highly organized six-layered structure with four major cortical neuron subtypes: corticothalamic projection neurons (CThPNs), subcerebral projection neurons (SCPNs), deep callosal projection neurons (CPNs), and superficial CPNs. Here, careful examination of multiple conditional knockout model mouse lines showed that the transcription factor FOXG1 functions as a master regulator of postmitotic cortical neuron specification and found that mice lacking functional FOXG1 exhibited projection deficits. Before embryonic day 14.5 (E14.5), FOXG1 enforces deep CPN identity in postmitotic neurons by activating
Satb2
but repressing
Bcl11b
and
Tbr1
. After E14.5, FOXG1 exerts specification functions in distinct layers via differential regulation of
Bcl11b
and
Tbr1
, including specification of superficial versus deep CPNs and enforcement of CThPN identity. FOXG1 controls CThPN versus SCPN fate by fine-tuning
Fezf2
levels through diverse interactions with multiple SOX family proteins. Thus, our study supports a developmental model to explain the postmitotic specification of four cortical projection neuron subtypes and sheds light on neuropathogenesis.
Synthetic gene circuits for preventing disruption of the circadian clock due to interleukin-1–induced inflammation
Authors: Pferdehirt Lara , Damato Anna R. , Dudek Michal , Meng Qing-Jun , Herzog Erik D. , Guilak Farshid
Published: May 2022

The circadian clock regulates tissue homeostasis through temporal control of tissue-specific clock-controlled genes. In articular cartilage, disruptions in the circadian clock are linked to a procatabolic state. In the presence of inflammation, the cartilage circadian clock is disrupted, which further contributes to the pathogenesis of diseases such as osteoarthritis. Using synthetic biology and tissue engineering, we developed and tested genetically engineered cartilage from murine induced pluripotent stem cells (miPSCs) capable of preserving the circadian clock in the presence of inflammation. We found that circadian rhythms arise following chondrogenic differentiation of miPSCs. Exposure of tissue-engineered cartilage to the inflammatory cytokine interleukin-1 (IL-1) disrupted circadian rhythms and degraded the cartilage matrix. All three inflammation-resistant approaches showed protection against IL-1–induced degradation and loss of circadian rhythms. These synthetic gene circuits reveal a unique approach to support daily rhythms in cartilage and provide a strategy for creating cell-based therapies to preserve the circadian clock.
Selective endocytosis of Ca
2+
-permeable AMPARs by the Alzheimer’s disease risk factor CALM bidirectionally controls synaptic plasticity
Authors: Azarnia Tehran Domenico , Kochlamazashvili Gaga , Pampaloni Niccolò P. , Sposini Silvia , Shergill Jasmeet Kaur , Lehmann Martin , Pashkova Natalya , Schmidt Claudia , Löwe Delia , Napieczynska Hanna , Heuser Arnd , Plested Andrew J. R. , Perrais David , Piper Robert C. , Haucke Volker , Maritzen Tanja
Published: May 2022

AMPA-type glutamate receptors (AMPARs) mediate fast excitatory neurotransmission, and the plastic modulation of their surface levels determines synaptic strength. AMPARs of different subunit compositions fulfill distinct roles in synaptic long-term potentiation (LTP) and depression (LTD) to enable learning. Largely unknown endocytic mechanisms mediate the subunit-selective regulation of the surface levels of GluA1-homomeric Ca
2+
-permeable (CP) versus heteromeric Ca
2+
-impermeable (CI) AMPARs. Here, we report that the Alzheimer’s disease risk factor CALM controls the surface levels of CP-AMPARs and thereby reciprocally regulates LTP and LTD in vivo to modulate learning. We show that CALM selectively facilitates the endocytosis of ubiquitinated CP-AMPARs via a mechanism that depends on ubiquitin recognition by its ANTH domain but is independent of clathrin. Our data identify CALM and related ANTH domain–containing proteins as the core endocytic machinery that determines the surface levels of CP-AMPARs to bidirectionally control synaptic plasticity and modulate learning in the mammalian brain.
Anomalous transport in high-mobility superconducting SrTiO
3
thin films
Authors: Yue Jin , Ayino Yilikal , Truttmann Tristan K. , Gastiasoro Maria N. , Persky Eylon , Khanukov Alex , Lee Dooyong , Thoutam Laxman R. , Kalisky Beena , Fernandes Rafael M. , Pribiag Vlad S. , Jalan Bharat
Published: May 2022

The study of subtle effects on transport in semiconductors requires high-quality epitaxial structures with low defect density. Using hybrid molecular beam epitaxy (MBE), SrTiO
3
films with a low-temperature mobility exceeding 42,000 cm
2
V
−1
s
−1
at a low carrier density of 3 × 10
17
cm
−3
were achieved. A sudden and sharp decrease in residual resistivity accompanied by an enhancement in the superconducting transition temperature were observed across the second Lifshitz transition where the third band becomes occupied, revealing dominant intraband scattering. These films further revealed an anomalous behavior in the Hall carrier density as a consequence of the antiferrodistortive (AFD) transition and the temperature dependence of the Hall scattering factor. Using hybrid MBE growth, phenomenological modeling, temperature-dependent transport measurements, and scanning superconducting quantum interference device imaging, we provide critical insights into the important role of inter- versus intraband scattering and of AFD domain walls on normal-state and superconducting properties of SrTiO
3
.
Actin-binding protein filamin-A drives tau aggregation and contributes to progressive supranuclear palsy pathology
Authors: Tsujikawa Koyo , Hamanaka Kohei , Riku Yuichi , Hattori Yuki , Hara Norikazu , Iguchi Yohei , Ishigaki Shinsuke , Hashizume Atsushi , Miyatake Satoko , Mitsuhashi Satomi , Miyazaki Yu , Kataoka Mayumi , Jiayi Li , Yasui Keizo , Kuru Satoshi , Koike Haruki , Kobayashi Kenta , Sahara Naruhiko , Ozaki Norio , Yoshida Mari , Kakita Akiyoshi , Saito Yuko , Iwasaki Yasushi , Miyashita Akinori , Iwatsubo Takeshi ,   Japanese Alzheimer’s Disease Neuroimaging Initiative (J-ADNI), Ikeuchi Takeshi ,   Japanese Longitudinal Biomarker Study in PSP and CBD (JALPAC) Consortium, Miyata Takaki , Sobue Gen , Matsumoto Naomichi , Sahashi Kentaro , Katsuno Masahisa
Published: May 2022

While amyloid-β lies upstream of tau pathology in Alzheimer’s disease, key drivers for other tauopathies, including progressive supranuclear palsy (PSP), are largely unknown. Various tau mutations are known to facilitate tau aggregation, but how the nonmutated tau, which most cases with PSP share, increases its propensity to aggregate in neurons and glial cells has remained elusive. Here, we identified genetic variations and protein abundance of filamin-A in the PSP brains without tau mutations. We provided in vivo biochemical evidence that increased filamin-A levels enhance the phosphorylation and insolubility of tau through interacting actin filaments. In addition, reduction of filamin-A corrected aberrant tau levels in the culture cells from PSP cases. Moreover, transgenic mice carrying human filamin-A recapitulated tau pathology in the neurons. Our data highlight that filamin-A promotes tau aggregation, providing a potential mechanism by which filamin-A contributes to PSP pathology.
Therapeutic strategies targeting uPAR potentiate anti–PD-1 efficacy in diffuse-type gastric cancer
Authors: Qin Long , Wang Long , Zhang Junchang , Zhou Huinian , Yang Zhiliang , Wang Yan , Cai Weiwen , Wen Fei , Jiang Xiangyan , Zhang Tiansheng , Ye Huili , Long Bo , Qin Junjie , Shi Wengui , Guan Xiaoying , Yu Zeyuan , Yang Jing , Wang Qi , Jiao Zuoyi
Published: May 2022

The diffuse-type gastric cancer (DGC) is a subtype of gastric cancer (GC) associated with low HER2 positivity rate and insensitivity to chemotherapy and immune checkpoint inhibitors. Here, we identify urokinase-type plasminogen activator receptor (uPAR) as a potential therapeutic target for DGC. We have developed a novel anti-uPAR monoclonal antibody, which targets the domains II and III of uPAR and blocks the binding of urokinase-type plasminogen activator to uPAR. We show that the combination of anti-uPAR and anti–Programmed cell death protein 1 (PD-1) remarkably inhibits tumor growth and prolongs survival via multiple mechanisms, using cell line–derived xenograft and patient-derived xenograft mouse models. Furthermore, uPAR chimeric antigen receptor–expressing T cells based on the novel anti-uPAR effectively kill DGC patient–derived organoids and exhibit impressive survival benefit in the established mouse models, especially when combined with PD-1 blockade therapy. Our study provides a new possibility of DGC treatment by targeting uPAR in a unique manner.
The dynamic atmospheric and aeolian environment of Jezero crater, Mars
Authors: Newman Claire E. , Hueso Ricardo , Lemmon Mark T. , Munguira Asier , Vicente-Retortillo Álvaro , Apestigue Víctor , Martínez Germán M. , Toledo Daniel , Sullivan Rob , Herkenhoff Ken E. , de la Torre Juárez Manuel , Richardson Mark I. , Stott Alexander E. , Murdoch Naomi , Sanchez-Lavega Agustín , Wolff Michael J. , Arruego Ignacio , Sebastián Eduardo , Navarro Sara , Gómez-Elvira Javier , Tamppari Leslie , Smith Michael D. , Lepinette Alain , Viúdez-Moreiras Daniel , Harri Ari-Matti , Genzer Maria , Hieta Maria , Lorenz Ralph D. , Conrad Pan , Gómez Felipe , McConnochie Timothy H. , Mimoun David , Tate Christian , Bertrand Tanguy , Bell James F. , Maki Justin N. , Rodriguez-Manfredi Jose Antonio , Wiens Roger C. , Chide Baptiste , Maurice Sylvestre , Zorzano Maria-Paz , Mora Luis , Baker Mariah M. , Banfield Don , Pla-Garcia Jorge , Beyssac Olivier , Brown Adrian , Clark Ben , Montmessin Franck , Fischer Erik , Patel Priyaben , del Río-Gaztelurrutia Teresa , Fouchet Thierry , Francis Raymond , Guzewich Scott D.
Published: May 2022

Despite the importance of sand and dust to Mars geomorphology, weather, and exploration, the processes that move sand and that raise dust to maintain Mars’ ubiquitous dust haze and to produce dust storms have not been well quantified in situ, with missions lacking either the necessary sensors or a sufficiently active aeolian environment. Perseverance rover’s novel environmental sensors and Jezero crater’s dusty environment remedy this. In Perseverance’s first 216 sols, four convective vortices raised dust locally, while, on average, four passed the rover daily, over 25% of which were significantly dusty (“dust devils”). More rarely, dust lifting by nonvortex wind gusts was produced by daytime convection cells advected over the crater by strong regional daytime upslope winds, which also control aeolian surface features. One such event covered 10 times more area than the largest dust devil, suggesting that dust devils and wind gusts could raise equal amounts of dust under nonstorm conditions.
Unraveling the physiochemical nature of colloidal motion waves among silver colloids
Authors: Chen Xi , Xu Yankai , Zhou Chao , Lou Kai , Peng Yixin , Zhang H. P. , Wang Wei
Published: May 2022

Traveling waves are common in biological and synthetic systems, including the recent discovery that silver (Ag) colloids form traveling motion waves in H
2
O
2
and under light. Here, we show that this colloidal motion wave is a heterogeneous excitable system. The Ag colloids generate traveling chemical waves via reaction-diffusion, and either self-propel through self-diffusiophoresis (“ballistic waves”) or are advected by diffusio-osmotic flows from gradients of neutral molecules (“swarming waves”). Key results include the experimental observation of traveling waves of OH
−
with pH-sensitive fluorescent dyes and a Rogers-McCulloch model that qualitatively and quantitatively reproduces the key features of colloidal waves. These results are a step forward in elucidating the Ag-H
2
O
2
-light oscillatory system at individual and collective levels. In addition, they pave the way for using colloidal waves either as a platform for studying nonlinear phenomena, or as a tool for colloidal transport and for information transmission in microrobot ensembles.
CERBERUS in the DARPA Subterranean Challenge
Authors: Tranzatto Marco , Miki Takahiro , Dharmadhikari Mihir , Bernreiter Lukas , Kulkarni Mihir , Mascarich Frank , Andersson Olov , Khattak Shehryar , Hutter Marco , Siegwart Roland , Alexis Kostas
Published: May 2022

This article presents the core technologies and deployment strategies of Team CERBERUS that enabled our winning run in the DARPA Subterranean Challenge finals. CERBERUS is a robotic system-of-systems involving walking and flying robots presenting resilient autonomy, as well as mapping and navigation capabilities to explore complex underground environments.
A Conserved Biosynthetic Gene Cluster Is Regulated by Quorum Sensing in a Shipworm Symbiont
Authors: Robes Jose Miguel D. , Altamia Marvin A. , Murdock Ethan G. , Concepcion Gisela P. , Haygood Margo G. , Puri Aaron W.
Published: May 2022

Bacteria play important roles as symbionts in animals ranging from invertebrates to humans. Despite this recognized importance, much is still unknown about the molecular details of how these relationships are formed and maintained.
Clinical Outcomes of Treated and Untreated C. difficile PCR-Positive/Toxin-Negative Adult Hospitalized Patients: a Quasi-Experimental Noninferiority Study
Authors: Hogan Catherine A. , Hitchcock Matthew M. , Frost Spencer , Kapphahn Kristopher , Holubar Marisa , Tompkins Lucy S. , Banaei Niaz
Published: May 2022

Clostridioides difficile
infection (CDI) is routinely diagnosed by PCR, with or without toxin enzyme immunoassay testing. The role of therapy for positive PCR and negative toxin remains unclear.
Supplemental Material: New age constraints support a K/Pg boundary interval on Vega Island, Antarctica: Implications for latest Cretaceous vertebrates and paleoenvironments
Authors: Roberts Eric M. , et al.
Published: May 2022

Figures S1–S7 and Tables S1 and S2.
Mathematical modelling of the most effective goal of cholesterol-lowering treatment in primary prevention
Authors: Soran Handrean , Adam Safwaan , Iqbal Zohaib , Durrington Paul
Published: May 2022

Objective

To compare quantitatively different recommended goals for cholesterol-lowering treatment in the primary prevention of atherosclerotic cardiovascular disease (ASCVD).

Design

Outcomes at pretreatment low-density lipoprotein (LDL) cholesterol concentrations from 2 to 5 mmol/L and 10-year ASCVD risk from 5% to 30% were modelled, using the decrease in risk ratio per mmol/L reduction in LDL cholesterol derived from randomised controlled trials (RCTs) of cholesterol-lowering medication.

Data source

Summary statistics from 26 RCTs comparing treatment versus placebo or less versus more effective treatment and 12 RCTs in which statin was compared with a higher dose of the same statin or with a similar statin dose to which an adjunctive cholesterol-lowering drug was added.

Setting

The different recommended goals are: (1) LDL cholesterol≤2.6 mmol/L (100 mg/dL); (2) LDL cholesterol≤1.8 mmol/L (70 mg/dL); (3) non-high density lipoprotein (HDL) cholesterol decrease of ≥40%; or (4) LDL cholesterol≤1.8 mmol/L (70 mg/dL) or decreased by ≥50% whichever is lower.

Participants

RCT participants.

Interventions

Statins alone or in combination with ezetimibe or proprotein convertase subtilisin/kexin type 9 inhibitors.

Main outcome measures

For each of the recommended therapeutic goals, our primary outcome was the number of events prevented per 100 people treated for 10 years (N100) and the number of needed to treat (NNT) to prevent one event over 10 years.

Results

At pretreatment LDL cholesterol 4–5 mmol/L, all four goals provided similar benefit with N100 1.47–16.45 (NNT 6–68), depending on ASCVD risk and pretreatment LDL cholesterol. With initial LDL cholesterol in the range 2–3 mmol/L, the target of 2.6 mmol/L was the least effective with N100 between 0 and 2.84 (NNT 35–infinity). The goal of 1.8 mmol/L was little better. However, reductions in non-HDL cholesterol by ≥40% or of LDL cholesterol to 1.8 mmol/L and/or by 50%, whichever is lower, were more effective, delivering N100 of between 0.9 and 9.33 (NNT 11–111). Percentage decreases in LDL cholesterol or non-HDL cholesterol concentration are more effective targets than absolute change in concentration in people with initial values of <4 mmol/L.

Conclusions

The LDL cholesterol target of 1.8 mmol/L is most effective when initial LDL cholesterol is >4 mmol/L. The time has probably come for the LDL cholesterol goal of <2.6 mmol/L to be abandoned.
Phase 2a randomised controlled feasibility trial of a new ‘balanced binocular viewing’ treatment for unilateral amblyopia in children age 3–8 years: trial protocol
Authors: Dahlmann-Noor Annegret Hella , Greenwood John A , Skilton Andrew , Baker Daniel , Ludden Siobhan , Davis Amanda , Dehbi Hakim-Moulay , Dakin Steven C
Published: May 2022

Introduction

Treatments for amblyopia, the most common vision deficit in children, often have suboptimal results. Occlusion/atropine blurring are fraught with poor adherence, regression and recurrence. These interventions target only the amblyopic eye, failing to address imbalances of cortical input from the two eyes (‘suppression’). Dichoptic treatments manipulate binocular visual experience to rebalance input. Poor adherence in early trials of dichoptic therapies inspired our development of balanced binocular viewing (BBV), using movies as child-friendly viewable content. Small observational studies indicate good adherence and efficacy. A feasibility trial is needed to further test safety and gather information to design a full trial.

Methods/analysis

We will carry out an observer-masked parallel-group phase 2a feasibility randomised controlled trial at two sites, randomising 44 children aged 3–8 years with unilateral amblyopia to either BBV or standard occlusion/atropine blurring, with 1:1 allocation ratio. We will assess visual function at baseline, 8 and 16 weeks. The primary outcome is intervention safety at 16 weeks, measured as change in interocular suppression, considered to precede the onset of potential diplopia. Secondary outcomes include safety at other time points, eligibility, recruitment/retention rates, adherence, clinical outcomes. We will summarise baseline characteristics for each group and assess the treatment effect using analysis of covariance. We will compare continuous clinical secondary endpoints between arms using linear mixed effect models, and report feasibility endpoints using descriptive statistics.

Ethics/dissemination

This trial has been approved by the London-Brighton & Sussex Research Ethics Committee (18/LO/1204), National Health Service Health Research Authority and Medicines and Healthcare products Regulatory Agency. A lay advisory group will be involved with advising on and disseminating the results to non-professional audiences, including on websites of funder/participating institutions and inputting on healthcare professional audience children would like us to reach. Reporting to clinicians and scientists will be via internal and external meetings/conferences and peer-reviewed journals.

Trial registration number

NCT03754153.
Reporting quality of clinical trial protocols: a repeated cross-sectional study about the Adherence to SPIrit Recommendations in Switzerland, CAnada and GErmany (ASPIRE-SCAGE)
Authors: Gryaznov Dmitry , von Niederhäusern Belinda , Speich Benjamin , Kasenda Benjamin , Ojeda-Ruiz Elena , Blümle Anette , Schandelmaier Stefan , Mertz Dominik , Odutayo Ayodele , Tomonaga Yuki , Amstutz Alain , Pauli-Magnus Christiane , Gloy Viktoria , Lohner Szimonetta , Bischoff Karin , Wollmann Katharina , Rehner Laura , Meerpohl Joerg J , Nordmann Alain , Klatte Katharina , Ghosh Nilabh , Taji Heravi Ala , Wong Jacqueline , Chow Ngai , Hong Patrick , McCord - De Iaco Kimberly A , Sricharoenchai Sirintip , Busse Jason W , Agarwal Arnav , Saccilotto Ramon , Schwenkglenks Matthias , Moffa Giusi , Hemkens Lars , Hopewell Sally , Von Elm Erik , Briel Matthias
Published: May 2022

Objectives

Comprehensive protocols are key for the planning and conduct of randomised clinical trials (RCTs). Evidence of low reporting quality of RCT protocols led to the publication of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist in 2013. We aimed to examine the quality of reporting of RCT protocols from three countries before and after the publication of the SPIRIT checklist.

Design

Repeated cross sectional study.

Setting

Swiss, German and Canadian research ethics committees (RECs).

Participants

RCT protocols approved by RECs in 2012 (n=257) and 2016 (n=292).

Primary and secondary outcome measures

The primary outcomes were the proportion of reported SPIRIT items per protocol and the proportion of trial protocols reporting individual SPIRIT items. We compared these outcomes in protocols approved in 2012 and 2016, and built regression models to explore factors associated with adherence to SPIRIT. For each protocol, we also extracted information on general trial characteristics and assessed whether individual SPIRIT items were reported

Results

The median proportion of reported SPIRIT items among RCT protocols showed a non-significant increase from 72% (IQR, 63%–79%) in 2012 to 77% (IQR, 68%–82%) in 2016. However, in a preplanned subgroup analysis, we detected a significant improvement in investigator-sponsored protocols: the median proportion increased from 64% (IQR, 55%–72%) in 2012 to 76% (IQR, 64%–83%) in 2016, while for industry-sponsored protocols median adherence was 77% (IQR 72%–80%) for both years. The following trial characteristics were independently associated with lower adherence to SPIRIT: single-centre trial, no support from a clinical trials unit or contract research organisation, and investigator-sponsorship.

Conclusions

In 2012, industry-sponsored RCT protocols were reported more comprehensively than investigator-sponsored protocols. After publication of the SPIRIT checklist, investigator-sponsored protocols improved to the level of industry-sponsored protocols, which did not improve.
Effectiveness and cost-effectiveness of dynamic bracing versus standard care alone in patients suffering from osteoporotic vertebral compression fractures: protocol for a multicentre, two-armed, parallel-group randomised controlled trial with 12 months of follow-up
Authors: Weber Annemarijn , Huysmans Stephanie M D , van Kuijk Sander M J , Evers Silvia M A A , Jutten Elisabeth M C , Senden Rachel , Paulus Aggie T G , van den Bergh Joop P W , de Bie Rob A , Merk Johannes M R , Bours Sandrine P G , Hulsbosch Mark , Janssen Esther R C , Curfs Inez , van Hemert Wouter L W , Schotanus Martijn G M , de Baat Paul , Schepel Niek C , den Boer Willem A , Hendriks Johannes G E , Liu Wai-Yan , Kleuver Marinus de , Pouw Martin H , van Hooff Miranda L , Jacobs Eva , Willems Paul C P H
Published: May 2022

Introduction

Patients with osteoporosis may suffer from a fracture after minimal trauma. Osteoporotic vertebral compression fractures (OVCFs) are among the most common fractures, often leading to substantial pain. There is a need for evidence-based conservative treatment to aid in the management of OVCFs. The objective of this randomised controlled trial (RCT) is to evaluate the effectiveness and cost-effectiveness of dynamic bracing in addition to standard care for improving quality of life (QoL) in patients suffering from an OVCF.

Methods and analysis

Ninety-eight postmenopausal women from two academic and four community hospitals with a recent symptomatic thoracolumbar OVCF will be randomised into either the standard care or dynamic bracing group. In the dynamic bracing group, the Spinova Osteo orthosis will be used in addition to standard care. Standard care comprises pain control with analgesics, physical therapy and osteoporosis medication. The primary outcome parameter is QoL 1 year after inclusion, as measured by the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO-41). Secondary outcome parameters are pain, pain medication used, functional disability, sagittal spinal alignment, recurrence rate of OVCFs and physical activity in daily life. A trial-based economic evaluation consisting of both cost-effectiveness analysis and cost-utility analysis will be performed based on empirical data obtained in the RCT. A process evaluation will assess the feasibility of dynamic bracing. All outcomes will be assessed at baseline, 6 weeks, 3 months, 6 months, 9 months and 12 months.

Ethics and dissemination

Ethical approval has been granted by the Medical Ethics Committee, University Hospital Maastricht and Maastricht University (METC azM/UM) (NL74552.068.20/METC 20-055). Patients will be included only after verification of eligibility and obtaining written informed consent. Results will be disseminated via the Dutch National Osteoporosis Patient Society and via publications and conferences.

Trial registration number

NL8746.
Factors associated with accessing and utilisation of healthcare and provision of health services for residents of slums in low and middle-income countries: a scoping review of recent literature
Authors: Park Ji-Eun , Kibe Peter , Yeboah Godwin , Oyebode Oyinlola , Harris Bronwyn , Ajisola Motunrayo M , Griffiths Frances , Aujla Navneet , Gill Paramjit , Lilford Richard J , Chen Yen-Fu
Published: May 2022

Objective

To identify factors associated with accessing and utilisation of healthcare and provision of health services in slums.

Design

A scoping review incorporating a conceptual framework for configuring reported factors.

Data sources

MEDLINE, Embase, CINAHL, Web of Science and the Cochrane Library were searched from their inception to December 2021 using slum-related terms.

Eligibility criteria

Empirical studies of all designs reporting relevant factors in slums in low and middle-income countries.

Data extraction and synthesis

Studies were categorised and data were charted according to a preliminary conceptual framework refined by emerging findings. Results were tabulated and narratively summarised.

Results

Of the 15 469 records retrieved from all years, 4368 records dated between 2016 and 2021 were screened by two independent reviewers and 111 studies were included. The majority (63 studies, 57%) were conducted in Asia, predominantly in India. In total, 104 studies examined healthcare access and utilisation from slum residents’ perspective while only 10 studies explored provision of health services from providers/planners’ perspective (three studies included both). A multitude of factors are associated with accessing, using and providing healthcare in slums, including recent migration to slums; knowledge, perception and past experience of illness, healthcare needs and health services; financial constraint and competing priorities between health and making a living; lacking social support; unfavourable physical environment and locality; sociocultural expectations and stigma; lack of official recognition; and existing problems in the health system.

Conclusion

The scoping review identified a significant body of recent literature reporting factors associated with accessing, utilisation and provision of healthcare services in slums. We classified the diverse factors under seven broad categories. The findings can inform a holistic approach to improving health services in slums by tackling barriers at different levels, taking into account local context and geospatial features of individual slums.

Systematic review registration number

https://osf.io/694t2.
Patient preferences and attitudes towards first choice medical services in Shenzhen, China: a cross-sectional study
Authors: Zhao Xinyu , Xiao Junhui , Chen Huida , Lin Kena , Li Xiaoman , Zeng Zhiwen , Huang Shuyun , Xie Zhikui , Du Jinlin
Published: May 2022

Objective

This study aimed to explore the characteristics of Shenzhen residents’ preferences and influencing factors regarding their first choice of medical institution at various medical levels, and to understand their attitudes towards community health services.

Design

Cross-sectional survey.

Participants

A total of 1612 participants at least 18 years of age were randomly sampled with stratification among 10 districts in Shenzhen. Data were gathered through a self-designed questionnaire. The effective questionnaire response rate was 93.05%. All patients participated in the study voluntarily, provided written informed consent and were able to complete the questionnaire.

Main outcome measures

We measured and compared the participants’ expected and actual preferences and influencing factors regarding their first choice of medical service at various medical levels.

Results

More than 50% of the participants preferred municipal and district hospitals as their first choice, and 27.5% chose medical institutions according to specific circumstances. Univariate analysis indicated that age, education, income, medical insurance, housing conditions and registered permanent residence were significantly associated with the actual and expected preferred first medical institution. The main factors influencing participants' actual and expected preferred medical institution differed. With the actual preferred first medical institution as the dependent variable, education, monthly income, medical technology, convenience and providers’ service attitude and medical ethics were the main factors (χ2=212.63, p<0.001), whereas with the expected preferred first medical institution as the dependent variable, occupation, Shenzhen registered permanent residence, education and medical technology were the main factors (χ2=78.101, p<0.001).

Conclusion

The main factors influencing participants’ preferred medical institution and their actual first visit differed. Patients with high education or income or registered permanent residence preferred high-level medical institutions for the first visit.
Multi-disciplinary Evaluation of Sexual Assault Referral Centres (SARCs) for better Health (MESARCH): protocol for a 1-year cohort study examining health, well-being and cost outcomes in adult survivors of sexual assault attending SARCs in England
Authors: O'Doherty Lorna , Carter Grace , Lutman-White Eleanor , Caswell Rachel , Jackson Louise J , Feder Gene , Heron Jon , Morris Richard , Brown Katherine
Published: May 2022

Introduction

Sexual violence is commonplace and has serious adverse consequences for physical and mental health. Sexual Assault Referral Centres (SARCs) are viewed as a best practice response. Little is known about their effectiveness and cost-effectiveness. Long-term data on the health and well-being of those who have experienced rape and sexual assault are also lacking.

Methods and analysis

This is a mixed-methods protocol for a 1-year cohort study aiming to examine the health and well-being in survivors of sexual violence after attending a SARC in England. Quantitative measures are being taken at baseline, 6 and 12 months. Post-traumatic stress (PTS) is the primary outcome (target N=270 at 12-month follow-up). Secondary measures include anxiety, depression, substance use and sexual health and well-being. Using mixed-effects regression, our main analysis will examine whether variation in SARC service delivery and subsequent mental healthcare is associated with improvement in trauma symptoms after 12 months. An economic analysis will compare costs and outcomes associated with different organisational aspects of SARC service delivery and levels of satisfaction with care. A nested qualitative study will employ narrative analysis of transcribed interviews with 30 cohort participants and 20 survivors who have not experienced SARC services.

Ethics and dissemination

The research is supported by an independent study steering committee, data monitoring and ethics committee and patient and public involvement (PPI) group. A central guiding principle of the research is that being involved should feel diametrically opposed to being a victim of sexual violence, and be experienced as empowering and supportive. Our PPI representatives are instrumental in this, and our wider stakeholders encourage us to consider the health and well-being of all involved. We will disseminate widely through peer-reviewed articles and non-academic channels to maximise the impact of findings on commissioning of services and support for survivors.

Trial registration number

ISRCTN30846825.